Lecture 1.

MOLECULE KINETIC-THEORY, ITS FUNDAMENTAL PRINCIPLES.

INTERMOLECULAR INTERACTIONS, VAN DER WAALS FORCES.

1. The world around us has a discrete structure (it is made of minute particles). It can
be divided into living and inorganic worlds. Constituent parts of the inorganic world (quarks,
atoms, molecules) strongly obey to physical laws. The hierarchy of the living world is
classified as cell, tissue, organ, organic system organism. In the mentioned systems of the
organic world certain phenomena are observed which currently can’t be explained. For
example, exchange of information between molecules, organs and organisms; principles of
preservation of the hereditary information, the molecular mechanisms of origination of
pathological processes, etc. The main subject of Medical Biophysics is to learn about the
structure and possible structural changes of biologically important molecules and supra-
molecular compounds at various pathological processes, to clarify the functions they fulfill in
the living organism and possible functional changes at various pathological processes.
The biopolymers of which are made up all living organisms, cells, etc, mostly include
nitrogen, carbon, hydrogen, oxygen, phosphorus, and sulfur. In the process of the vital
activity of organisms the ions of Na+, K+, Ca2+, Mg2+, Cu2+ are of great importance and some
other ions of a little less importance. The human organism contains H-60%, O-26%, C-11%,
N-2.5%, Ca-0.2%, P-0.13%, S-0.13%, Na-0.08%, Cl-0.03%, Mg-0.01%. The content of other
substances is less than 0.01%. Living organisms have the following molecular structure:
proteins, nucleic acids, carbohydrates, lipids, vitamins, hormones, cofactors. Proteins are
mostly made of amino acids of 20 types and nucleic acids are made of nucleotides of 5 types.
2. Interaction between uncharged material particles (atoms, molecules) are realized
by weak, nonvalent-forces, which are of attractive and repulsive types. At large distances
particles mainly attract each other and at small distances (when distances are of the order of
molecule sizes) they predominantly repel each other. The dependence of the potential
energy U(r) on

the distance between particles is presented in Fig.1.

In the general case
U(r)=Ur(r)+Ua(r) (1.1)
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The potential energy of the repulsion forces is positive ( U r ( r ) > 0) and that of the
attraction forces is negative ( U a ( r ) < 0)
The minimum point of function U(r) corresponds to the intermolecular distance r=r0,
which corresponds to the equilibrium distance. It can be determine from the condition
U ′(r ) = 0 . Knowing function U(r), the interaction force between molecules can be found
dU(r )
F(r ) = − . (1.2)
dr
From (1.2) it follows that U(r ) = − ∫ F(r )dr .
Constituent parts of molecules (atoms) are electrically charged particles (electrons,
protons). Depending on the distribution of electric charge in them, molecules are divided
into polar and non-polar types.
Polar are the molecules in which centers of distribution of positive and negative
charges are shifted. Non-polar are the ones in which centers of distribution of positive and
negative charges coincide. Polar molecules are permanent dipoles.
The distribution of the electric charge in the molecule is characterized by the degree
of its polarization, which is described by the dipole moment. Figuratively, the neutral polar
molecule is represented by a system of a pair of opposite charges which are equal in
magnitude and are at some distance l from each other (Fig,2)

According to this definition the dipole moment μ is given by formula μ=|q|l.

Let us consider the interaction forces between molecules. Since molecules may be
electrically charged or may contain charged groups, they can interact by electrostatic forces.
The energy of interaction is determined by formula
1 q q
U= ⋅ 1 2, (1.3)
4πε 0 εr
where r is the distance between the charged groups q1 and q2, and ε is the dielectric
permittivity and ε0=8.85·10-12 C·V-1·m-1 is the electric constant.
In the neighborhood of neutral pH negative are aspartic acid, glutamic acid and
phosphorus groups of nucleic acids. Positive are lysine, arginine, imidazole ring of histidine,
etc.
The energy of electrostatic interaction of of charged groups depends on the micro
surroundings of the charged groups. For example, near the protein surface contacting with
water (ε=80) energy is less than within the protein globule (ε=2 ÷ 5). Stipulated by that, the
energy of electrostatic interaction is about -40…-400 kJ/mole.
For biological systems of special interest are the interaction forces between neutral
particles, which are called Van-der-Waals forces. These forces play an important role in the
formation of liquid and solid aggregative states, in the creation of biopolymers, etc. Van-der-
Waals forces are of attractive nature and posses a small radius of action.
Depending on the fact if the interacting molecules possess a constant dipole moment
or acquire one due to the polarization of the electron shells, the following types of Van-der-
Waals forces are distinguished
a) Dispersion interaction
 3
The attractive interaction forces between neutral, non polar groups are called dispersion
interaction. The dispersion interaction is stipulated by the attraction of dipoles produced by
the instantaneous displacement of electron clouds in atoms /instantaneous dipole moments/.
The energy of interaction of dispersion interaction is determined by formula
3 I1I 2 α1α 2
U dis = − , (1.4)
2 I1 + I 2 r 6
where I1 and I2 are the ionization potentials of interacting groups, α1 and α2 are the
polarizabilities of those groups. The energy of dispersion interaction is about -4…-40
kJ/mole.
b) Dipole-dipole (orientational) interaction
The attractive forces acting between neutral, polar groups, which are stipulated by the
interaction of constant dipoles are called dipole-dipole interaction. Their energy of
interaction is determined by the formula
1 µ12 µ 22
U dd = − , (1.5)
6πε 0 kT εr 6
Where T is absolute temperature, k=1.38·10-23 J/K is the Boltzmann constant. μ1 and μ2 are
the constant dipole moments of the uncharged groups.
c) Dipole-induced dipole (induced) interaction
A constant dipole can induce a dipole moment in the neighboring non-polar
molecule, and a dipole-induced dipole interaction is resulting. The energy of this type of
interaction is determined by the following formula
1 αµ 2
U di = − , (1.6)
2πε 0 εr 6
where μ is the constant dipole and α is the polarizability of the non polar group.
Let us explain the physical meaning of polarizability. Suppose a neutral, non-polar molecule

is placed in an external electric field of strength E . Under the action of that field a
redistribution of electric charges of the molecule will take place, which will lead to
polarization of the molecule and it will acquire a dipole moment. If the field is not too
strong, the acquired dipole moment will be directly proportional to the strength of the
electric field: µ ~ E or µ = αE . Coefficient α represents the polarizability of the non polar
group. It dimension [α]=Cm2/V=A2s4/kg. The energy of the dipole-dipole and dipole-induced
dipole interactions is about -0.4… -4 kJ/mole. Formulas (1-4)-(1-6) show that the Van-der-
1
Waals interaction forces acting between neutral molecules is proportional to , but the
r6
1
energy of the electrostatic interaction according to formula (1.2) is proportional to .
r
Therefore, the Van-der-Waals interaction forces are important only at small distances.
Generalizing all above things we can represent the energy of the Van der Waals
interaction forces in the form
A
Ua = − . (1.7)
r6
It can be theoretically shown that the repulsive forces acting between molecules at
small distances are represented in the form
 4
B
Ur = n . (1.8)
r
In general n = 8 ÷ 13 . In (1.7) and (1.8) A and B are positive constants and depend on the
chemical composition and structure of the interacting molecules. n is nostly taken equal to
12.
Taking into account formulas (1.7) and (1.8), formula (1.1) can be written in the form
A B A B
U( r ) = − 6 + n or U(r ) = − + . (1.9)
r r r 6 r12
Hydrogen bond. Hydrogen bonds play an important role in biological systems.
Hydrogen bonds emerge between an electronegative atom of O,N,S, or P and the hydrogen
atom, which is covalently bound with one of this atoms. The energy of the hydrogen bond is
about -12.6… -33.6 KJ/mole. The hydrogen bond can’t be explained only by the electrostatic
interaction of atoms, it is of very complicated nature and the creation of the bond can only
be explained and described by means of quantum mechanics. The hydrogen bond possesses a
number of properties, which mostly are not characteristic for other types of physical
interactions. Let us mention a few of them:
a) substantial space direction
b) saturation of interaction
c) a certain length of the bond, which depends on the medium and elements making the
bond
For example, the length of the O-H bond in ice makes about 1.77A0
3. Particles in living and inorganic systems make irregular, thermal, chaotic motion,
which depends on the aggregative state of the matter. The existence of molecules and their
chaotic motion can most convincingly be proved by the Brownian motion and diffusion,
which is the spontaneous, that is, without any action of external factors, mixing of different
substances. The fact that substances can be found in different physical states is stipulated by
the nature of motion of their constituent particles.
The intensity of the thermal, chaotic motion depends on the temperature of the
medium and is proportional to the quantity RT. At temperatures of vital activity of living
organisms RT is about -48 j/mole and is much less than the activation energy needed for
various biochemical processes. Therefore, this energy can’t have a substantial, decisive
influence on biochemical processes taking place at equilibrium conditions. However, if the
living system is found at extreme conditions (stress, improper ecological conditions, etc) the
thermal energy can to a certain extent affect the course of biochemical processes, which can
lead to some change in the activation energy of biological processes.
 5
LECTURE 2
AGGREGATIVE STATES OF MATTER

We saw that there exist attractive and repulsive forces between constituent particles
of matter (atoms, molecules), whose intensity depends on the mutual position of those
particles: it means particles posses potential energy. Particles are in an incessantly motion,
therefore they possess also kinetic energy.
It can be qualitatively asserted that the attractive forces tend to bind the molecules
into a single whole but the presence of the kinetic energy hinders this process. Thus, the
system is simultaneously influenced by both biding and pulling apart (tearing) factors. The
result of these competing factors depends on their relative intensity. If the intensity of the
tearing factor is greater than that of the binding one, the substance turns in the gaseous state.
In the opposite case the substance is in the solid state. If the intensities of these factors are of
the same order the substance is in the liquid state.
The quantitative measure of the concept of “intensity” is the particle kinetic and
potential energies. If the total kinetic energy is greater than the potential energy, then the
molecules spontaneously scatter in the space available to them. Thus, we are having a gas,
which tends to expand.
When the gas is compressed, its density increases, correspondingly the intermolecular
distances decrease. Therefore, the absolute value of the potential energy grows (Fig.1), which
follows also from formula (1.1). As a result, there comes a point (value of the intermolecular
distances), when the system total potential energy exceeds the kinetic energy. In such a
system the molecules are no more free, but are bound together by certain forces, and thus
the substance finds itself in the liquid or solid state. In such a process the matter rather passes
over into the liquid state. However, such a transition (process) is possible only in the case
when the kinetic energy of molecules is not too great, that is, the gas temperature is not too
great. The matter is that the minimal value of the potential energy has a lower limit.
Therefore, at quite high temperatures it can’t be larger of the kinetic energy, that is, the
substance can’t be liquefying.
At lowering the pressure the opposite process is taking place: the liquid transforms
into gas.
So, usually, matter can exist in three aggregative states: solid, liquid, and gaseous.
Relatively recently, the fourth aggregative state has been detected: plasma. Plasma is
the basic form of existence of matter in the Universe. It represents a system consisting of
electrons, nuclei and ions having been constituent parts of atoms.
In the gaseous state the matter preserves neither its shape, nor volume since the
binding forces keeping together its molecules are practically absent. The gas occupies the
whole available volume, so saying gas volume we mean the volume of the vessel containing
it. Gas molecules are in a state of permanent chaotic (disorderly) motion, each molecule
moving uniformly, in straight line, and only at colliding with other molecules it changes
direction. At that, the mean distance covered between two successive collisions (the free
path) much exceeds the molecule sizes.
At certain conditions, for gas contained in a vessel the sizes of molecules and their
collisions can be neglected. Only collisions with the walls of the vessel are taken accounted
of. At such assumptions the gas particles are considered as material point not interacting with
each other. At such simplification the gases called perfect.
 6
Perfect gases are described by Mendeleyev Clapeyron equation having the form:
PV=νRT (2.1)
Where P, V, T and ν are correspondingly the gas pressure, volume, temperature and amount
J
of moles, and R is the universal gas constant. It is equal to 8.31 . The isotherm of an
mol ⋅ K
ideal gas has the following form

If we take into account the attractive and repulsive forces of interaction between gas
molecules, then such gases by their properties are close to real gases and are well described
by Van der Waals equation having the form
a
(P + ν 2 )(V − νb) = νRT . (2.2)
V2
‘a’ and ‘b’ are called Van der Waals constants and for different gases they have different
values.
Pa ⋅ m 6 m3 .
‘a ‘is measured in and ‘b’ is measured in
mol 2 mol
Parameter ‘a’ characterizes the attractive forces acting between molecules and ‘b’
characterizes the total volume of the gas and repulsive forces. The isotherm of a real gas
described by equation (2.2) has the following form

The range ac correspond to liquids because it describes the incompressibility of the matter
(great pressures are needed to change the volume a little). The section bd correspond to the
gaseous state. It reminds one about the isotherm of an ideal gas. The wavelike behavior in
section ab doesn’t correspond to any real behavior of a gas. Actually here a phase transition
takes place between gas and liquid.
In a liquid state, matter preserves its volume and not its shape, that is, it can flow
(possesses flowability).
According to the established view, the thermal motion in liquids takes place in this
way. Each molecule oscillates during a time period of about 10-11 s around some equilibrium
position. Then at times jumps up into a new equilibrium position and oscillates there. The
subsequent positions of the molecule are apart from each other at a distance of the order of
sizes of molecules. So, the liquid molecules simply slowly wander in the whole volume of the
liquid.
Since the liquid density by far exceeds that of the gas, that means, the liquid
molecules are much closer to each other, so the structural peculiarities of molecules greatly
affect the structure and properties of the whole liquid.
 7
For example, because of a peculiar distribution of electric charge in the water
molecule, each water molecule can create 4 hydrogen bonds with neighboring water
molecules, producing local space hexagonal structures. The liquids are isotropic, that is, in all
spatial directions they have the same properties.
At present there is no equation of state that could precisely describe properties of
liquids in the whole temperature range.
Solids are substances that preserve not only their volume but also their shape.
According to their internal structure, solids can be crystalline and amorphous.
The crystalline bodies or, simply, crystals, have a regular internal structure. Crystal
particles (atoms, ions or molecules) make small amplitude thermal oscillations around certain
points, which are the nodes of the crystal lattice. The nodes are distributed in the space in a
periodical and strongly symmetrical way. The jumps of particles from one equilibrium
position into another take place quite rarely, and therefore, diffusion in solids takes place
very slowly. The crystal lattice tells nothing about the sizes of particles, the distances they
are apart. It simply describes the mutual positions of centers of particles in the space. In Fig.
3 a small portion of the crystal lattice of NaCl is depicted.

Fig. 3
The outward feature of every crystal is its regular geometrical form. They have smooth, as if
polished faces, which are regular polygons and the angles between faces and edges are
certain constant numbers. The most conspicuous manifestation of the symmetry of internal
structure is the dependence of physical properties of the crystal on the chosen direction in it.
The dependence of the physical properties of crystal on the chosen direction in it is called
anisotropy. From the point of view of kinetic theory, the anisotropy of crystals is caused by
the difference of distances between particles and consequently different interactions in
different directions.
Many substances in a crystalline state having the same chemical composition,
depending on conditions can produce several different types of crystalline structures. For
example, it is has been shown that there are 10 modifications of ice; carbon can exist in the
form of graphite, diamond, carbyne and fullerene.
Crystalline bodies at the given conditions have a certain melting temperature. For
example, under normal conditions ice melts at 00C.
Contrary to crystals, amorphous bodies are isotropic; their physical properties are
independent of the chosen direction. This fact testifies that amorphous bodies don’t have a
regular internal structure. The immediate consequence of amorphous bodies not having a
regular internal structure is the lack of a melting temperature. When an amorphous body is
heated, parallel to receiving an amount of heat, its temperature continuously increases, it
gradually softens and transforms into a liquid. If an amount of heat is taken from that liquid,
its temperature continuously decreases, and the liquid transforms to a solid amorphous body.
 8
Physical properties of an amorphous body depend both on its state and the nature of the
external influences. The higher is the temperature of the amorphous body and the longer is
the external action, the closer are its properties to that of a liquid. And, vice versa, at lower
temperatures and short time actions, the amorphous body behaves like a solid crystalline
body.
Liquid crystals. The duality of properties of amorphous bodies, that is, possessing of
properties of both solids and liquids is characteristic also for the liquid crystals. Liquid
crystals by their structural properties occupy an intermediate place between crystalline solids
and liquids. In the liquid crystals in one direction a regular arrangement of particles is
observed, and in that direction they are anisotropic.
Nowadays, many organic substances of biological origin are known which produce a
liquid crystalline state. Examples are DNA, collagen, medullar substance, cytoplasm, etc.
Properties of liquid crystals can substantially be changed with the help of very weak
external factors (temperature, electric and magnetic fields, etc), due to which they are widely
used in technology, household, medicine. The importance of liquid crystals is great especially
in medicine and biology. The further investigation of their properties will allow clarifying
the mechanisms of a number of biological processes.
Structure of water, its physicochemical properties
Water is one of the most important chemical compounds if not the most important. It
is the main constituent of the human organism and the environment of its vital activity.
Physical properties of water substantially differ from that of other liquids, what explains the
participation of water in processes taking place in the living and inorganic worlds. In the
terrestrial water, there always are dissolved compounds, mainly CO2, which are available
from the atmosphere.
If we compare physicochemical characteristics with that of other liquids, we will see
that water has the greatest melting and boiling temperatures, specific heat, latent heat of
evaporation and fusion, surface tension, etc. The mentioned anomalous properties of water
are stipulated by the fact that its molecules interact with great forces. For comparison, the
values of latent specific heats (r) of evaporation are brought for a number of liquids at
pressure 1atm. From the table it follows, that the latent specific heats of evaporation of water
by far exceeds that of many other liquids. It is well known that it directly depends on forces
of intermolecular attractive forces and is given by the energy necessary to transfer to the unit
volume of the liquid to overcome the attractive forces between them and bring it into the
gaseous state
Liquid r(cal/g)
water 540
methanol 263
ethanol 204
H-propanol 164
acetone 125
benzol 94
chloroform 59
As we have mentioned, water possesses specific properties, which are caused by the
features of its structure. The structures of the condensed (liquid and solid) and gaseous states
of water depend on the valency status of the oxygen atom in it. In general, oxygen is in
 9
bivalent state and with hydrogen comprises a valency saturated compound. In the gaseous
state, oxygen in water molecule is in the bivalency state and makes with the hydrogen atom
a valency saturated bond creating a triatomic mutually free water molecule.
In the ice, as well as in liquid water oxygen is in tetravalency state, which is produced
due to the transferring of one of two 2p electrons into the 3s state. As a result, an sp3
hybridized state is produced, when the four unbound electrons in the condensed state
interacting with the neighboring hydrogen atoms form a tetrahedron with four bonds, two
of which are strong representing a covalent bond and the two others represent a relatively
weak hydrogen bond. Due to these interactions, different molecular spatial lattices of water
can be formed.
With the help of X-ray structure analysis currently 10 of structural types of ice are
detected, which are realized at low temperatures and high pressures.
Under normal conditions the structure produced by water (ice) represents a spatial
lattice formed by the interactions of hexagonal rings. A hexagonal ring is formed by 6 oxygen
atoms at the corners of the ring and 12 hydrogen atoms, 6 of which are in the plane of the
hexagonal ring between oxygen atoms and the other six next to nearest between oxygen
atoms at different sides of the ring plane. Therefore, the hexagonal ring of the ice structure is
formed by 6 water molecules. The hexagonal rings are bound together due the tetrahedron of
valency bonds and are linked together by hydrogen bonds which is aligned by the O-H+…O-
axis.
Let us consider the behavior of the hexagonal structures at ice melting and water
vaporizing.
Using the thermodynamical parameters of water (latent heat of melting 64 kJ/mole,
latent heat of evaporation 500 kJ/mole) and the value of the energy of the hydrogen bond in
water (19kJ/mole) we can conclude that at the transition ice-water only 32% of the hydrogen
bonds are destroyed. Since in the ice structure for releasing one H2O water molecule 2
hydrogen bonds must be destroyed, then at melting of ice the number of free triatom water
molecules makes about 16% and to each free H2O molecule there corresponds about 6 bound
molecules.
Consequently, in the liquid phase of water together with the gas-like molecules there
exist also hexagonal parts of the ice structure: Concentrations of the ‘gas-like’ and ‘ice-like’
structural parts are approximately equal.
Summarizing we can say that at melting of ice 32% of hydrogen bonds are broken,
and as a result of witch the monolithic crystal brakes to microcrystals (clusters) in between
of which free unbound gas-like water molecules are located. Thus, the liquid phase of water
represents a mixture of the molecular structural elements of ice and free water molecules.
The liquid-vapor transition leads to the destruction of the hexagonal clusters and to the
increase in the number of free water molecules.
All the biochemical processes taking place in the living organism are realized in the
water environment. Water is the universal medium through which most probably the
transfer of bioinformation between the individual cell molecules or its structural elements is
carried out. From this viewpoint the investigation of the water structure and its possible
changes at different pathological processes represents a big interest.
 10
The above mentioned anomalous physicochemical properties of water are caused by
the structure of water molecule (by the distribution of electric charge within the molecule),
as a result of which they, after being bound together by hydrogen bonds, produce clusters.

Hydrophobic and Hydrophilic Interactions

Water plays a great role in the formation and stabilization of the structure of
biopolymers. It is known that those biopolymers contain polar and non-polar functional
groups, which can interact with water molecules by electrostatic and Van der Waals forces
simultaneously creating hydrogen bonds.
Any system, including biological ones, tends under given conditions to create such a
structure that the free energy of the system is minimal. Therefore, from the energetic
viewpoint it is advantageous that some functional groups of biopolymers directly bind with
water and some others, vice versa, avoid the direct interaction with the water molecules and
come together expelling water from them producing compact carbon formations. For
example, in proteins, water can compete with the polar amino acid remnants in creating
hydrogen bonds, as a result of which the polar amino acid remnants tend to get bound by
hydrogen bonds not only with the free water molecules but also with the water molecules
having produced a hexagonal structure. As a result of such interactions, the water hexagonal
cluster structure undergoes some changes, and the free energy of the system changes. At the
same time, the protein non-polar amino acid remnants avoiding interaction with water
(which would lead to the increase of the free energy) approach each other reducing as much,
as possible the direct contact of the non-polar amino acid remnants with water molecules.
Consequently, due to the intermolecular Van der Waals interaction a definite biopolymer
structure is formed in the water medium having a minimal free energy, whose polar
functional groups are mainly bound with water molecules and non-polar ones avoiding an
interaction with the water molecules are pulled together forming a compact structure having
a minimal square area. It is thanks to the mentioned circumstance that, for example, some
proteins produce compact structures, which are called globules.
On the basis of this Kausman introduced the concepts of the hydrophilic and
hydrophobic interactions. They are not new interaction forces, but represent the same Van
der Waals interaction forces between water and organic compounds containing polar and
non-polar groups. If as a result of the interaction between the investigated compounds and
water the system free energy decreases, then these compounds or functional groups prefer to
be surrounded by water molecules, they ‘like’ to enter into contact with water molecules,
they are hydrophilic. And if as a result of the interaction between the investigated
compounds and water the system free energy increases, then the compounds or functional
groups prefer to come together, expelling water molecules from within themselves, they
‘don’t like’ to enter into contact with water molecules, they are hydrophobic. In this way, on
the basis of the condition of minimum of the free energy of the system the spatial structure
of the biopolymer with the given primary structure is formed. Although between different
functional groups of biopolymers other types of interaction or bond are operating too (for
example, hydrogen bonds, disulfide bonds, etc.), the hydrophilic and hydrophobic
interactions play a great role in the formation and stability of their secondary and tertiary
structures.
11
 12
Lecture 3.
TRANSPORT PHENOMENA
Due to the thermal motion and interaction of particles densities of different parts of
the system, temperatures, particle velocities, etc., are getting equal. It is realized via
phenomena called diffusion, thermoconductivity and internal friction. These processes are
unified under the term of transport phenomena.
In the equilibrium state, temperature at all points must be the same. The shift in
temperature in some part of the body leads to a thermal motion in all parts of the system in
order to equalize it. The heat transfer caused by this is called thermoconductivity.
In the equilibrium state the densities (concentrations) of all constituent parts of the
body at all points is the same. Deviation of density from its equilibrium value leads to
movements in the body trying to equalize them. The material transfer caused by this is called
diffusion.
In the equilibrium state different parts of the system are resting relative to each other.
Their relative motion is opposed by viscosity. The viscosity forces are stipulated by the
processes of momentum transfer between different layers in case of their relative motion. As
a result a transfer of momentum of ordered motion of molecules is taking place.
Description of transport phenomena
If as a result of the transport phenomenon an equalization of some quantity Φ is takes place,
dΦ
then its variation in a unit length on the x direction is represented by . It describes the
dx
rate of changing of quantity Φ (its change on a unit length).. This quantity is called gradient
of Φ. It is a vector and directed towards the increase of Φ If variation of quantity Φ along x
axis takes place uniformly, then gradient is determined by
dΦ Φ 2 − Φ1
= .
dx ∆x
∆x is the distance between points 1 and 2.
direction
of flux

Φ1 Δx Φ2

x
Fig. 1
Flux of quantity Φ is the transferred amount of Φ through a unit area in unit time and is
denoted by I Φ . The direction of the flux of quantity Φ coincides with the direction of
decrease of that quantity. In all transport phenomena there exists a general rule
dΦ
I Φ = −α Φ . (3.1)
dx
where α Φ is the coefficient of proportionality and is determined by the type of the transport
dΦ
phenomenon. is directed towards the increase of Φ . The flux of Φ is directed opposite
dx
dΦ
to and always tends to decrease it. (Hence the ‘-‘sign in (3.1)). If there is no an external
dx
source keeping the gradient of Φ constant, after a while it will disappear. But if there is such
 13
dΦ
a source and = const , the transport may continue long and it is called a stationary
dx
transport..
Diffusion. Diffusion takes place when there is an inhomogeniety in the molecule number or
density.
The transport of only one of the components is called self-diffusion. The flux of
dN
diffusion is determined by expression I n = . Equation (3.1) takes the form
Sdt
I n = −D  .
dn
(3.2)
 dx  P, T
This is called Fick’s law.
dρ
I M = −D  , (3.3)
 dx  P, T
1
D is diffusion coefficient. Calculations show that in gases D = λv , where λ is the free path
3
and v is the mean velocity of molecules.
Thermal conductivity. Suppose temperature changes from point to point along X axis, while
in the plane perpendicular to that axis it is constant everywhere (Fig. 2)

Fig. 2
Equation (3.1) takes the form (Fourier law)
dT
I Q = −χ (3.4)
dx
χ is called coefficient of thermal conductivity.
Viscosity (internal friction). Suppose change in velocity of a gas or liquid occurs in X
direction. In the plane, perpendicular to that axis, velocity is constant everywhere.

Fig. 3
∆p
By definition, I p = . Here ∆p is the amount of momentum transferred across S during
∆t ⋅ S
∆p
time ∆t . According to Newton’s second law, = F . So, according to equation (3.1) the force
∆t
of internal friction per unit area, shear strain, (flux of momentum transfer) operating between
different layers will be
F dv
= −η , (3.5)
S dx
 14
η is called coefficient of dynamical viscosity or dynamical internal friction and depends on liquid
(gas) properties. η numerically equals to force acting on the surface area of 1 m2 in case of a unit
velocity gradient.
For liquids equation (3.5) is called Newton equation. The force acting on square area S
will be
dv
F = −η S . (3.6)
dx
The unit of measurement of η is determined from equation (3.6) and represents
N ⋅s kg
[η] = = . The force of internal friction decelerates the faster moving layers and
m 2 s⋅m
accelerates the slower moving ones.
Together with the coefficient of dynamical viscosity the kinematical coefficient of
viscosity (ν) is used too. It is determined by formula (ρ is the liquid density).
η
ν= . (3.7)
ρ
By their viscous properties liquids are divided into newtonian and non-newtonian types.
Liquids are called newtonian if their coefficient viscosity depends only on their type and
B
temperature. The dynamical viscosity is described very well by formula η = Ae T , where
coefficients A and B are determined only by type of the liquid.
Liquids are called non-newtonian if their coefficient of viscosity depends not only on their type
and temperature but also on the regime of the liquid flow, in particular, on the velocity gradient
 dv  . In the general case,
 
 dx 
n
 dv 
F÷  , (3.8)
 dx 
where n characterizes the mechanical properties of the liquid at the given flow regime.
An example of a non-newtonial liquid is suspension. It can be represented as liquid in
which the not interacting particles are distributed uniformly. Properties of such a system
first of all depend on liquid coefficient η0. In the general case the viscosity of the system
depends on the concentration of dissolved particles and their shape. At small concentrations
that dependence has the following form:
η = η0 (1 + kc), (3.9)
where k depends on the geometrical form (shape, sizes) of the particles.
For example, for the spherical particles
4
k = 2.5Vs = 2.5 ⋅ πR 3 ,
3
where R is the particle radius.
If during the flow the shape or sizes of particles change, then η changes too. A typical
example of a non Newtonian liquid is the blood.
Laminar and turbulent flows.
The flow of a gas or liquid is laminar if the layers of the gas or liquid flowing at
different velocities don’t mix with each other and flow in parallel streams. At laminar flow of
a liquid, the velocity of the liquid in the direction perpendicular to the tube axis changes by
the quadratic law, and the curve connecting the heads of velocity vectors represents a
parabola (Fig. 4).
 15

Fig. 4
The liquid velocity as depending on the distance x from the tube axis is determined
by formula
 x 2 
v = v 0 1 − , (3.10)
 R2 
 
where R is the tube radius and v0 is the velocity of the liquid particles on moving the axis of
the tube.
At the certain value of the stream velocity, which depends on the properties of the
gas or liquid and tube radius, the flow becomes turbulent. The smaller the tube radius is, the
greater are velocities at which the flow becomes turbulent.
At the turbulent flow the velocities of liquid points at different parts of the liquid
volume change randomly. In this case, the velocity profile is no more parabolic.
The nature of the liquid flow is determined by the Reynolds number (Re). In the case
of the flow through a cylindrical tube
2Rvρ
Re = , (3.11)
η
where v is the mean velocity of the liquid flow through the tube cross section, R is the tube
radius.
If Reynolds number is less than the critical value Recr=2300, the liquid flow is
laminar. If Re>Recr, the flow becomes turbulent.
As a rule, the flow of blood through vessels is laminar. However, sometimes it
becomes turbulent. For example, it happens near places of ramification (branching) of vessels
because of the increase of the velocity of the flow, at places where the vessels are locally
narrowed (thrombus), etc.
Poiseuille’s formula. The blood vessels represent cylindrical tubes of different
diameters, so let us consider the laminar flow of a liquid through a cylindrical vessel. The
distribution of velocities of the liquid, when it flows through such a vessel, is represented in
Fig. 4. If the difference of pressures on distance l is Δp, then in the case of a stationary
laminar flow the liquid volume passing in unit time through the cross section of the tube is
given by the Poiseuille’s formula
πR 4 ∆p
Q= . (3.12)
8η l
At the given pressure difference, the liquid volume transferred through the tube is greater at
smaller viscosity η and greater tube radius. Poiseuille’s formula is valid only at the laminar
8ηl
flow. Quantity W = is called hydraulic resistance. In terms of W, (3.12) can be written
πR 4
as Δp=WQ. Quantity Q is often called volume velocity. From formula (3.12) it follows that
the drop in the blood pressure depends on the volume velocity of the blood flow and
strongly depends on the vessel radius. For example, the decrease of 20% of the tube radius
leads to the double or more increase in Δp.
 16
A small change in the lumen of the blood vessels considerably affects the pressure
difference Δp. Therefore, the drugs regulating human blood pressure directly affect the
lumen of the blood vessels.
Limits of applicability of Poiseuille’s formula.
1.laminar flow
2. homogeneous liquid
3.straight hard vessels
4. liquid flow far from the source of disturbance.

Lecture 4
THERMODYNAMICS

A system consisting of a large number of particles is called a thermodynamic system.

Consequently, every living system, cell or organ generally can be considered as a
thermodynamic system.
Thermodynamics is the part of physics which matter, phenomena without
considering the behavior of particles, regarding the body as one whole.
The subject of thermodynamics is to investigate the properties of phenomena and
bodies with the help of macroscopic parameters (which are quantities describing the system
taken as a whole) on the basis of general laws called thermodynamic principles without
clarifying the molecular mechanisms of the given phenomenon or the structure of the given
body.
Thermodynamics relies on three principles. The first one represents the law of
conservation of energy as applied to heat phenomena, the second one determines the
direction of the course of thermodynamic processes and the third one limits the possible
thermodynamic processes by asserting the inaccessibility of the absolute zero temperature.
The main macroscopic parameters describing the thermodynamic system are the
volume (V), pressure (P), temperature (T) and mass (m). The equilibrium state is the state
which is described by macroscopic parameters not depending on time, that is, the
macroscopic parameters remain constant.
The transition of a system from one equilibrium state to another is called process.
The processes when the system remains in its equilibrium state the whole time is
called a quasi-static process.
Work in thermodynamics. Suppose the system expanding does a work. For simplicity,
suppose the expansion has taken place by amount dx at constant pressure (Fig. 1)

Fig. 1
According to the definition of mechanical work:
dA = Fdx cos θ = pSdx = pdV . (5.1)
 17
For example, find the work done by 1 mole of perfect gas in a isothermal process
(T=const), when gas expands from volume V1 to V2
RT
dA = pdV = dV
V
V2 V 2
RT V
A= ∫ dV = RT ∫ dV = RT ln 2 .
V1 V V1 V1
V
For ν moles of gas it will be νRT ln 2 .
V1
In an isochoric process A=0. In an isobaric process A = p( V2 − V1 ) = p∆V .
Heat or amount of heat. Experiment shows that at contact of 2 bodies, their
temperatures become equal, a flow of heat from the warmer body transfers to the colder
body. Factually, heat represents energy in the form of chaotic motion of particles. We denote
it by Q and its change dQ.
The sum of the kinetic energy of particles and their potential energy of interaction is
called internal energy. We denote it by U and its infinitesimal change by dU.
I principle of thermodynamics. If a system is given amount of heat Q and it has done
work A, its internal energy changes by amount ∆U and according to the I principle of
thermodynamics
Q= ∆U+A (5.2)
In the differential form expression (5.2) can be written
dQ= dU+dA (5.3)
II principle of thermodynamics. As we already have mentioned, II principle of
thermodynamics determines the direction of thermodynamic processes. There are several
equivalent formulations of II principle of thermodynamics.
Claussius statement: Heat can’t transfer spontaneously from a cooler body (T1) to a hotter
body (T2) (T1< T2).
Thomson statement: Its impossible to realize such a cyclic process whose only result would
be conversion of heat into work through cooling of a body.
The thermodynamic process is reversible if the thermodynamic system can be returned to its
initial state without a waste of energy and/or changes in the surrounding medium
The thermodynamic process is irreverible if the thermodynamic system can’t be returned to
its initial state without a waste of energy and/or changes in the surrounding medium
Quasi-static processes are always reversible.
It is known that the heat transferred to a body in some process is a function of
process, that is, Q is not a function of state (mathematically, dQ is not a complete (total)
differential).
Functions of state are called all those quantities whose change doesn’t depend on the
way the process is run but only is determined by the difference of its values at the beginning
and end of the process. For example, internal energy is a function of state. Work and amount
of heat aren’t. Analysis show that at stationary processes though Q does not represent a
function of state, the ratio dQ/T does, in other words, it is a complete differential. The
function whose differential dQ/T is, is called entropy (S). So
dQ
dS = (5.4)
T
 18
2 dQ
∆S = S 2 − S1 = ∫ , (5.5)
1 T
where S2 and S1 are entropy values at the initial and final states of the system. So, entropy is a
function of state.
II principle of thermodynamics can be stated also through entropy.
Isolated are systems which don’t contact with surrounding bodies in the material or
energetic sense.
In processes proceeding in isolated systems entropy remains constant or increases.
Thus, processes in isolated systems, if initially not in equilibrium, are irreversible.
Consequently, if as a result of some processes an isolated system comes to an
equilibrium state, its entropy reaches a maximum value. Since an isolated system always
comes to an equilibrium, its entropy must increase.
F=U-TS is called free energy. It is a function of state. If the system goes to equilibrium, its
internal energy and free energy reaches the minimum value. This is also is a consequence of
the second principle of thermodynamics.
The physical sense of entropy can be explained on the basis of molecular kinetic
theory. In the general case entropy is determined by the degree of disorder of the particles
making it up.
Boltzmann has shown that entropy is related to the thermodynamic probability (W)
through the following formula
S=klnW, (5.6)
where k is the Boltzmann constant. k=1.38·10 J/K. Thermodynamic probability W
-23

represents the number of microstates through which the given macroscopic state is realized.
Let us clarify the concepts of the microstate and macroscopic state in more detail.
Suppose we have a system consisting of N1 particles which can occupy one of N possible
positions in the space.
A macroscopic state of this system represents a state, where the N1 particles occupy an
arbitrary set of N1 positions from possible N positions, specifically which positions, is not
essential. The given macroscopic state can be obtained in different ways. N1 particles can be
arranged in N positions in different ways and each arrangement represents a microstate and
they all represent the same macroscopic state. Using combinatorial calculus we ca find the
number of microstates, which determine the same macroscopic state
N!
W= . (5.7)
( N − N1 )!
If particles are identical, then
N!
W= (5.7a)
N1! ( N − N1 )!
Let us note that Boltzmann formula (5.6) goes for any system in regardless of the type of
processes in it (stationary or not stationary). From that formula it follows that the more is
system ordered (the more less is the number of microstates realizing the given macroscopic
state), the less is entropy of the system. Entropy, representing a physical quantity which
characterizes the degree of disorder in the system, tends to a a maximum value at the state of
equilibrium. Consequently, a secluded isolated system tending to an equilibrium state
reaches to the maximum value of entropy at the equilibrium state.
 19
Entropy and Information. The connection between entropy and information can be
understood with the help of following arguments.
Suppose we know the macroscopic state of a system, so that we know its volume,
pressure, temperature, chemical composition and the external fields acting on it with certain
accuracy. For each macroscopic state there exists a system of microstates (W). All microstates
corresponding to the given macroscopic state have the same probability. Our knowledge
about the system would be complete if we know which microstate it is in. Let us calculate
the amount of information we have to obtain from the given system in the given
macroscopic state in order to determine its microstates uniquely.
Imagine a series of experiments has been carried out the microstates have been
determined (actually it is impossible). Before the experiment, the probability that the system
was in the given microstate is P=1/W. After the experiment it equals to 1. The amount of
information acquired, which is determined by formula (5.8)
1
I = log 2 = − log 2 P
P
will be
1
I = − log 2 = log 2 W (5.9)
W
Now compare equation (5.9) with equation (5.6).
It follows that both entropy and information are determined by W. They coincide
with accuracy of a constant factor. Thus, entropy of the system represents the amount of
information that is lacking for its complete description. In general, quantities I and S are
essentially identical. In the case of entropy and information we are encountered with the
same situation what exists with energy (E) and mass (m). According to equation E=mc2, E
and m are differing by the constant factor c2.
In order to transit from the amount of information (bit) to entropy (unit of entropy) it
is necessary to transit from the logarithm with base 2 to the logarithm with base e (natural
logarithm) and multiply by k. Evaluations show that S(unit of entropy)=(kln2)I (bit). As we
know, the organism of an adult person contains about 1013 cells. If we assume that there are
no two identical cells, the amount of information needed to make a man from that many
cells will be
I = log 2 1013!= 1013 log 2 1013 ≈ 4 ⋅ 1014 bit.
Consequently, the change in entropy in making an ordered structure, that is, a man,
from separate cells would be
∆S = −k ln 2 ⋅ 4 ⋅ 1014 = −3.8 ⋅ 10 −9 entropy unit.

Living organisms as open systems

All the biological systems are thermodynamically open systems, which exchange
energy and matter with the surrounding bodies. In some cases, when such processes taking
place in the living organism are investigated, which proceed in times much shorter than the
time of its observation (for example, in chemical transitions) or the time of theirs observation
is much shorter than the time of systems interaction with the surrounding bodies, the living
organism can be regarded as a closed system. From this viewpoint, processes in the inorganic
world and living organisms will be described by the same laws.
 20
Consequently, in certain exclusive cases, the biosystem can be described by the laws
of thermodynamic laws of stationary processes. However, mostly, it is impossible to neglect
the influence of foreign bodies on the given living or inorganic system. In such cases for
describing the systems, it is necessary to use the laws of non-equilibrium thermodynamics.
In spite of different processes taking place in the living organisms, they can be found in
stationary states. Let us note, that although in stationary states the system interacts with
surrounding bodies, the parameters it describing do not change in time.
Suppose the time of observation is such that the living organisms can be taken as
being in a stationary state. Although it is in a stationary state, in living organism irreversible
processes take place (diffusion, chemical reactions, etc) and, consequently, its entropy
increases, entropy of the system remains constant. The total change in entropy of the system
ΔS can be represented as a sum of two terms
∆S = ∆S i + ∆S e , (5.10)
where ΔSi represents the change in entropy due to the non-equilibrium processes and ΔSe is
the change in entropy due to the interaction of the system with the external bodies.
For non-equilibrium processes ΔSi>0 and for stationary processes ΔS=0. So,
ΔSe= ΔS–ΔSi=–ΔSi <0.
This expression can be interpreted in this way. The entropy obtained by the living system in
the form of matter or energy is less than the entropy of products which have left the living
organism.
As we have mentioned, in the equilibrium state entropy adopts its maximum value.
The stationary state has been investigated by Prigojin. According the principle suggested by
him, the non-equilibrium processes occurring in the system in a stationary state (diffusion,
chemical reactions, etc) proceed in such a way that the entropy increment is minimal. It
means that the system can’t leave its stationary state due to its own non-equilibrium
processes. Even if due to small deviations (fluctuations) it departs a little from its stationary
state, the internal processes tend to decrease dSi/dt and return it again to the initial stationary
state
In the general case, the living organism represents an open thermodynamic system,
which exchanges material and energy with the surrounding bodies. It is a developing system,
and can’t exist in the same stationary state.
Suppose the time of observation dt is so small that the state of the system can be
regarded as stationary. In the stationary system dS=0 and thus S=const, dSi>0 and dSe<0. If the
system organism-surrounding environment as a whole is considered as an isolated system, its
entropy must increase, though organism entropy must be constant. Since entropy describes
the degree of disorder of the system, so we can conclude the order of the system is preserved
thanks to the decrease in the order in the surrounding environment.
At certain pathological processes the entropy of a biosystem can increase (dS>0). In
this case the stationarity of the system is broken, and the degree of disorder of the system
increases and as a result, the system may be unable to come to a new stationary state. Such a
situation arises, for example, at tumorous transformation of the cell. An irregular chaotic
growth of the number of cells takes place, and a result the system is unable to reach a
stationary state.
For an infinitesimal time dt expression (5.10) can be written dS=dSi+dSe, whence we
have
 21
dS dSi dSe
= + . (5.11)
dt dt dt
dS
In a stationary state (S=const) = 0 and so
dt
dSi dS
=− e . (5.12)
dt dt
From expression (5.12) it follows that at the normal functioning of the living
organism the negative sign in the rate of changing in entropy due to the internal processes
equals to that due to the material and energetic exchanges with the surrounding
dSi
environment. According to Prigojin principle, > 0 and at the same time adopts its
dt
minimal value.
dS
From (5.11) it follows that quantity − e has a minimal value too. So, generalizing,
dt
we can say that at the stationary state the rate of changing of entropy of the surrounding
environment is minimal too.
 22
Lecture 4
MODELLING OF BIOPHYSICAL SYSTEMS. PHARMAKOKINETIC MODEL
The living organism is an extremely complex system to be described wholly in
detail. Therefore various models are being suggested to study its different aspects.
Modeling is the substitution of an object (process, phenomenon) because of its
complexity by an object similar to it but much more simple. Practically in all topics of
biophysics various models are considered, for example, liquid mosaic model of membrane,
model of formation of the potential of action (Hodgkin-Huxley model), model of cardio
vascular system (Frank model), model of contraction of muscle and others.
These are the requirements put to the model
1. Adequacy of the model to the object
2. The limits of applicability of the model must be set up. It means the conditions must
be defined at which the proposed model corresponds to the researched object. No
model gives a complete description of the object.
Basic stages of modeling
1. Gathering of primary information
2. Formulation of the problem
3. Foundation of basic assumptions
4. Creation of the model, its investigation
5. Checking of the adequacy of the object to the real object. Establishment of the
framework of validity of the model.
Physical model. It has the same physical nature as the object. For example, the flow of the
blood in vessels is modeled by the flow of a fluid in tubes with hard or elastic walls.
In modeling of electrical processes in the heart, the latter is taken as a current dipole
generator. In modeling transport processes artificial membranes are used.
Physical models are also artificial organs, the artificial kidney is the model of kidney,
cardiostimulator is the model of processes taking place in the cardiac sinus node, and the
artificial berthing apparatus is a model of lungs.
Biological models represent biological objects which are convenient for experimental studies.
For example, the nerve axon squid became a successful model for the laws of origination and
propagation along the nerve stem of the action potential.
Mathematical model. It is the depiction of processes in real objects with the help of
mathematical equations, generally with differential equations.
For the realization of the mathematical model often computers are used.
By changing coefficients in differential equations or by adding new terms for
accounting for this or that feature, theoretically new objects can be created possessing new
properties, produce new preparations with more effective drug actions.
With the help of computers complicated differential equations can be solved, the
system behavior can be predicted, the course of the disease can be followed, the efficiency of
a pharmacological preparation can be investigated, etc.
These are certain the requirements put to the model
1. Adequacy of the model to the object
2. The limits of applicability of the model must be set up
 23
For example, while the model of a perfect gas quite accurately describes the state of the
real gas only at very high temperatures and low pressures, the Van der Waals model is
adequate for a broader range of pressures and temperatures.
Or, the liposome model is adequate for the study of lipid permeability while for the
electrogenesis is not good.
Pharmacokinetic model
For the description of kinetics of the changing of concentration of drug substances being
discharged from the organism the pharmacokinetic model is proposed.
Let us find the law of changing of concentration of a drug substance different ways and
parameters of its introduction and discharge from the organism. We will make the following
admissions
1) We will not consider the system of organs through which the drug passes in
succession.
2) We will not consider the molecular mechanisms of processes
3) The processes of introduction and discharge are reduced to rates

1-st way. Single introduction of a drug preparation: injection. (Fig.a). Organism is

represented as a system of volume V. A drug preparation of mass m0 is introduced in it after
which begins the process of it elimination. The rate of elimination p is directly proportional
to its mass in the organism
𝑑𝑑𝑑𝑑
= −𝑘𝑘𝑘𝑘.
𝑑𝑑𝑑𝑑
𝑚𝑚 = 𝑚𝑚𝑒𝑒 −𝑘𝑘𝑘𝑘 . k is the drug removal constant of the organism
Concentration of the drug substance in the organism (for instance, in the blood) c=m/V will
be
𝑐𝑐 = 𝑐𝑐0 𝑒𝑒 −𝑘𝑘𝑘𝑘 c0 is the initial concentration.
2-nd way. Continuous introduction of a preparation at constant rate: infusion (Fig b) (this
corresponds to connecting the patient to a dropping device. In this case the change of the
drug mass is determined not only by the rate of its elimination, but also by the rate of its
introduction Q. Q is the amount of drug introduced into organism per unit time. So we have
𝑑𝑑𝑑𝑑
= 𝑄𝑄 − 𝑘𝑘𝑘𝑘.
𝑑𝑑𝑑𝑑
Solving this differential equation we take into account that at t=0 mass m=0, thus
𝑄𝑄
𝑚𝑚 = (1 − 𝑒𝑒 −𝑘𝑘𝑘𝑘 ).
𝑘𝑘
 24
Q
(1 − e − kt ) . When 𝑡𝑡 → ∞, 𝑐𝑐 → .This is the stationary
𝑄𝑄
For concentration we get c =
kV 𝑘𝑘𝑘𝑘

concentration of the drug after a long time of its introduction. Choosing a proper rate of drug
introduction Q=kVcopt, (level of copt is less of the level of toxicity), we will achieve that a time
period later an optimal concentration will be established, which is necessary for the
therapeutic effect. The optimal concentration can be achieved in the organism instantly if
the first method is combined with the second one.
3-rd way. If the two mentioned methods are combined,
𝑄𝑄 1 𝑄𝑄
𝑐𝑐 = − � − 𝑚𝑚0 � 𝑒𝑒 −𝑘𝑘𝑘𝑘 .
𝑘𝑘𝑘𝑘 𝑉𝑉 𝑘𝑘
Mathematical Models Of Population Growth
The processes taking place in communities of living organisms are taking place in
time and in the space. Sometimes the synchronism of processes in all parts of the given space
is also acceptable.
Model of the natural growth of population: Malthus model
Real System. Population of the same species (for example, microorganisms, hares, etc)
Life processes are taking place with their different manifestations.
Major admissions.
1. Only processes of reproduction and death take place with rates directly proportional
the population of the species
2. Biochemical and physiological processes are not allowed for
3. There is no competition for food and space
4. There are no predators, only one population is considered
Malthus Law
x is population at time t, R is rate of reproduction, γ is reproduction factor
dx
S is the rate of natural death, σ is the factor of natural death, is the rate of
dt
population growth, ε is growth factor then R = γ ⋅ x and S = −σx
The corresponding differential equation will have the following form
dx
= ( γ − σ) x
dt
at the initial moment t = 0 x = x 0 or
dx
= εx where ε = γ − σ
dt
x x 0 ⋅ eεt
=
Depending on time, population changes by the exponential law.
Analysis of solution
a) ε > 0 ; γ − σ > 0; γ>σ
Infinite growth of population by the exponential law.
ε > 0 model is adequate for a definite period of

x0
t
 25

According to this model, in the case of (ε > 0 ) the population will grow infinitely if only
natural death is allowed for. However, if, ε < 0 the population decreases and if ε = 0 , it
remains constant.
ε<0 ε=0
x x

x0 x0

t t

Verhulst model (Pierre Francois Verhulst)

Now suppose there exists competition within the given species. It provides an
additional cause for death within it. The equation for the population number x becomes
= (γ − σ )x − δx 2 .
dx
dt
The solution of this non linear equation with the initial condition at t=0, x=x0 is
x 0ε
x(t) =
(ε − δx 0 )e − εt + x 0 δ
The graph of the solution this solution is

We see that after a little while the number of species is stabilized tending to a
constant xmax value.
Now let us discuss the “predator-prey” model, where two types of objects are
considered: prey: “hare” (population denoted by x(t)) and predator: “lynx” (population
denoted by y(t)). The first object feeds on the plant feed and the second one on the preys.
The resulting mathematical model is a system of nonlinear equations. The model is called
Lotka–Volterra model.
The equations of the model are
 dx = εx − αxy,
 dt

 dy = θxy − βy.
 dt
ε β
y stationary = x stationary =
α θ
ε is the natural rate of the increase of the hare population and β is the natural rate of
natural death of lynx population and α is the rate of the encounter of the two species. The
stationary solution is achieved when the time derivatives are put zero. But an interesting
point is what happens at the small deviations from the stationary values.
x (t ) = x stat. + U max sin εβ t
 26
y(t ) = y stat. + Vmax sin ( εβ t + ϕ0 )
. We see periodical oscillations of populations by frequency ω = εβ around the
stationary values and there is a phase shift between them ϕ 0 . This type of changing was
observed in Canada by the number of furs of the animals in 1845-1935.

Here is the graph of x and Y dependence on time

In this model the spontaneous emergence of self oscillating processes is a manifestation self
regulation or self organization in open complex dynamic systems. The science investigating
the general regularities in the formation of ordered macrostructures in time and space is
called synergy. The formation of self organized systems takes place due to the cooperative
interactions between the subsystems in the system.

Lecture 6
STRUCTURE AND PHYSICAL PROPERTIES OF BIOPOLYMERS
Polymers are compounds in which large number of identical or not identical
atomic groups are connected by chemical bonds in long chains following each other in
some definite succession.
According to their origination, polymers are divided into natural and synthetic
types. Among natural polymers are (India) rubber, cellulose, starch, proteins, etc. Since
in living systems nucleic acids and proteins due to their structure have many important
functions, let us study their structure in more detail.
Structure of nucleic acids. Nucleic acids are divided into two classes:
deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Under in vivo and in vitro
conditions DNA creates linear or closed , circular double helical structures. RNA, which
 27
in living organisms is encountered in 4 different modifications (rybosomic, matrix,
transport and virus). Under in vivo and in vitro conditions DNA creates linear double
helical structures, closed circular or cross like structures, in which nitrogenous bases of
the same or different chains can pair wise produce hydrogen bonds.

The double helical structure of DNA. X-ray analysis of membranes and

oligonucleotide crystals made of DNA have shown that depending on the relative
humidity of the environment, ionic force and nucleotide sequence DNA molecule can
exist in double helical conformations characterized by different helix parameters.
Currently experimentally discovered and investigated are right (A,B,C etc) and left (Z,Z´
etc) helical forms of DNA (Fig.2). Let us note that in in vivo conditions DNA molecule
exists in the B form, which is characterized by the following properties parameters:
molecule diameter 20 A0, distance between two neighboring bases along the chain
3.4±0.2 A0, to a single coil there come 10.4±0.1 pairs of nitrogenous bases, which
depending on the nucleotide sequence and medium properties are twisted relative each
other by an angle about 36±4o. the two bases are oriented almost parallel to each other.
Because of the thermal motion, bases can shift maximum by 3o (Fig.2).

Fig. 2
A B Z
In the helix state, the pair of the nitrogenous bases with a certain probability (10-
5
) can open or close. Form B of DNA is often called the native structure of DNA. DNA is
in native state in the 5 ÷ 8 range of pH. The increase or decrease of pH leads to the
breakdown of the helical structure.
 28

Fig. 3
A B Z

The hydrogen bonds, intramolecular and intermolecular Van der Waals forces
(hydrophilic and hydrophobic forces) functioning between the pair of complementary
nitrogenous bases play an essential role in the stabilization of the double helical
structure of DNA. In modeling, the DNA molecule can be considered as a one-
dimensional nonperiodical crystal.
As a solid body, the DNA molecule is one-dimensional because at considering it
as a crystal, its elementary cell (pair of nitrogenous bases) interact only with the 2
neighboring cells. The molecule is nonperiodical since it consists of two types of
elementary cells: AT (adenine-thymine) and GC (guanine-cytosine). Properties of such
a one-dimensional nonperiodical crystal essentially differ from those of crystals made up
of low-molecular substances. In the general case, the DNA molecule represents a
specific physical system, and its clarification of its physical properties would allow to
understand the biological functions of the DNA molecule in the living organism and to
explain its capabilities in biological systems.
Denaturation of DNA. Of the physical processes proceeding in the DNA
molecule, relatively well investigated is the process of denaturation (melting if caused by
heating, helix-coil transition). To get a better picture of it, let us consider the process of
melting of a low molecular substance, for example of ice. It is well known that water-ice
transition takes place at 00C (2730K) temperature and unless the whole ice has
transformed into water, system temperature doesn’t change. In Fig. 4 the graph of
dependence on t of a physical parameter, namely specific heat, is presented in the
vicinity of 00C

Fig.4
From the graph it can be seen that at heating the ice, its temperature at first
grows till 00C, after that, although the system continues getting heat, its temperature
doesn’t change. When the whole ice has transformed into water at 00C, C changes
making a jump, and afterwards, if heated, its temperature increases.
During further heating, C almost remains constant. Therefore, the ice-water
transition can be described by one parameter: melting temperature.
 29
Let us consider denaturation of the DNA molecule. The double helix of the DNA
molecule under certain conditions, for example, at raising the temperature, changing
pH, gets destroyed up to separating into two chains. This process is depicted in Fig.5.

a) The state of the complete helix

b) Partially denaturized state
c) Completely denaturized state
In the process of denaturation, the sequence of nitrogenous bases (the primary
structure) is not changing (chemical bonds are not destroyed). Destroying are the
intermolecular hydrogen bonds acting between the two helixes.
The one thread DNA molecule chains, which are produced due to denaturation,
represent elastic polymer chains. Such chains are described by the model of the freely-
connected chain. The distribution of distances between their ends is Gaussian, and it
bears the name of Gaussian or statistical coils. In the denaturized or coiled state, the
distance between the neighboring nitrogenous bases is 6.8 A0, which is twice greater
than in the double helix state. Under certain conditions the melting of the DNA molecule
is irreversible. With decreasing temperature the complementary bases of the chain are
connected by hydrogen bonds producing double helical segments. Thus, summarizing
the stated above we can conclude that the denaturation of the DNA molecule
represents a transition from the state of the ordered (crystal) helix to the state of
disordered coiled (liquid) state. Let us study the dependence of a physical quantity (for
example, viscosity ηof a solution) on

Fig. 6
Experiments show that depending on the ionic force of the medium, starting from
some temperature viscosity decreases and in the state of complete denaturation stays
nearly constant. Therefore, denaturation of the DNA molecule (melting) is not occurring
at a constant temperature. So, to describe the process of denaturation it is necessary to
have at least to parameters. Conventionally, these are called melting temperature and
interval.
The molar mass of the DNA molecule is about 107 ÷ 109 Daltons. If it were a fully
extended double helix (had a rod like structure), it would have a length of 5 mcm.
 30
However, by the method of light scattering it has been proved that on physiological
conditions it has a size of 0.5 mcm. From these data we can conclude that the double
helical structure of the DNA molecule in certain places is broken forming denaturized
segments. For such structures, the dependence of the molecule sizes on the molar
mass is found by Dotty-Rice-Makhich formula, which for the native DNA molecule has
the following form
R = 2.7 ⋅ 10 −9 M 0.58 (7.1)
If DNA were a perfect coil, for it would be R = A ⋅ M 0.5 and if it were a stiff rod then
R = A ⋅ M . Thus, as it follows from formula (7.1), in the native state the DNA molecule
has some intermediate structure.
Hydrodynamical investigations have revealed that beginning from some gradient
DNA molecules break into small pieces without changing the double helical structure.
For this reason, in dealing with a DNA molecule with a great molecular mass,
one must be very careful using capillaries with as big diameters, as possible and the
solution pour in or out slowly.
Thanks to investigations, for the characteristic viscosity of DNA the following
formulas have been obtained. If the DNA molar mass is within 3 ⋅ 10 5 ÷ 2 ⋅ 10 6 interval,
the characteristic viscosity which characterizes viscosity of one molecule and is defined
by formula (7.2)
η − η0
[η] = lim , (7.2)
c → 0 cη 0
will be determined by formula (7.3)
[η] = 1.05 ⋅ 10 −7 M1.32 . (7.3)
And if the molar mass is in the interval 2 ⋅ 10 6 ÷ 1.3 ⋅ 108 , then
[η] = 6.9 ⋅ 10 −4 M 0.7 . (7.4)
Let us note that if the DNA molecule in the native state were a Gaussian coil, the
dependence of [ η] on M would be determined by f
[η] = KM 0.5 ÷ 0.7 . (7.5)
And if it represented a stiff rod, then
[η] = KM1.8 . (7.6)
By comparing formulas (7.3), (7.4) with formulas (7.5),(7.6), one can conclude that in
physiological conditions the DNA molecule takes up an intermediate position between
‘coil’ and ‘rod’. If molar mass M is greater than 2·106 Daltons, molecule behavior is
closer to a coil and at smaller masses the DNA molecule behaves like a rod.
Denaturation of the DNA molecule can be investigated by different physical
methods: spectroscopic, calorimetric, hydrodynamical, etc. A relatively simple method of
investigation is the measurement of absorption of light by the solution of DNA molecule
in the ultraviolet range as depending on temperature. In the general case DNA absorbs
light at wavelengths smaller than 310 nm, one of maximums of which comes at λ=260
nm. It is known that because of denaturation, the amount of absorption increases. The
increment at the state of full denaturation makes 30-40% of the initial absorption. This
effect is called hyperchromatic effect and is caused by the elimination of the Van der
Waals interaction forces between bases acting in the perpendicular direction to their
plane.
According to Lambert Berr law, the relationship between the intensities of the
incident to the sample (I0) and emergent I beams is given by formula
I = I 0 e −εcd , (7.7)
 31
where c is solution concentration, d is the thickness of the solution and ε is the molar
coefficient of absorption, which usually is measured in units l·Mol-1cm-1l. The physical
I
quantity ln 0 = A is called optical density, and according to (7.7), is determined by
I
formula A=εcd.
In the case of DNA, assuming that the increment in absorption is directly
proportional to the number of destroyed hydrogen bonds one can construct the curve of
denaturation (melting) representing the dependence of the share of the destroyed
bonds on temperature. If A(T) represents the optical density of DNA at an arbitrary
temperature T, and A1 and A2 are its values at the completely helical and completely
denaturized states of the DNA molecule, then
A ( T ) − A1
A 2 − A1
will represent the number of monomers which are in the denaturized state: 1-ν
A ( T ) − A1
I−ν = . ((7.8)
A 2 − A1
νis called helicity, that is, the share of monomer units which are in the helical state.
N
ν= 1
N
N1 is the number of monomer units of the DNA molecule which are in the helical state,
and N is the total number of monomers in the DNA molecule.
In Fig. 7 the graph of denaturation of the DNA molecule is depicted.

Fig. 7
It can be seen from Fig.7 that denaturation is not taking place at one definite
temperature as is the case with the melting of ice, thus the process of denaturation
essentially differs from the process of melting of low-molecular crystal bodies.
DNA and cancer. It is known that the DNA molecule represents the carrier,
keeper and transmitter of the hereditary information of the living organisms.
Investigations of recent years have testified that the hereditary information is not coded
only by the sequence of nucleotides of the DNA molecule. Apart from being the material
carrier of information, DNA is surrounded by holographic field, which is also a carrier of
information. Currently a new direction of genetics is being developed: Wave Genetics.
Now we consider the role of the DNA molecule in the originatation of cancer. For the
give organism the cancerous cell is not a foreign cell although it ‘behaves’ like a foreign one. In
the mature organism, the process of division is under the strict control though in different tissues,
for example in the brain, it is generally prohibited. Beginning from a moment, cell stops
following the ‘rules’ and begins to divide uncontrollably, that is, it transforms into a
 32
cancerous cell. Note, that this property is transferred to its generations. A situation is
created when we have ‘anomalous’ cells, but the immune system, which actively fights
foreign viruses and bacteria, isn’t recognizing them as foreign cells.
Where are this ‘anomalous’ cells taken from. Since their ‘bad behavior’ is
transmitted across generations, so it is natural to think that the DNA molecule has
undergone certain changes and therefore the cell has changed.
In the general case, such an approach is not correct, because it has been proven
that in a multicellular organism cells are able to abruptly change the information which
determines their behavior without changing the DNA structure. In many cases, the
differentia of the cells is caused by the change in the activity of genes, at which the
primary structure of DNA remains unchanged.
If we admit that cancer emerges due to the break of differentia of cells, we
encounter a number of difficulties. In particular, experiment shows that cancer can be
produced also due to the external influences, for example, at infecting the animal by a
virus (oncovirus). Later it was shown that the emergence of cancer can’t be always
explained by the virogenetic theory. For example, in many cases cancer can emerge
under the action of physical and chemical factors of different natures. Many compounds
are known (carcinogens) which can produce cancer. Later numerous experiments
revealed the first cause of the tumorous transformation of the cell is hidden in its genetic
material, in DNA. And finally, in 1979, experimentally was proven the genetic nature of
cancer, which was stipulated by DNA. Acting on DNA carcinogens change something
in its structure (mutation) and as a result, the normal cell is transformed into a
cancerous one. If the described view is correct, then by injecting the DNA separated
from a patient having cancer to a normal person, cancer can be produced in him.
Experiments proved the correctness of this idea.
Since the human DNA is transformed, so there exists an oncogen section which
is responsible for the emergence of a tumor. In a short time the sequence of nucleotides
of about 30 oncogens was discovered and investigated. Scientists believe that these
genes are responsible for the development of cancers of all types found in humans and
animals. Later it turned out that for each oncogen there exists its normal ‘counterpart ‘,
the normal gene, which is called proto-oncogene.
The proto-oncogene as such is not dangerous. From the viewpoint of molecular
genetics both oncogen and proto-oncogene represent ordinary structural genes, that is,
each of them carries information about the structure of a certain protein.
In a multicellular organism, each cell strictly obeys the information signals that
reach it. One of the most important of them is the information about the reproduction
(division).
What is the difference between the ‘bad’ oncogene and harmless, and even
useful, protoncogene. At present a number of mechanisms are known which transform
a protoncogene to an oncogene. It can be a point mutation or a chromosome
transformation, which leads to a protoncogene shifting to another chromosome. And
how does an oncogene work? An oncogene makes the cell DNA divide in a continuous
and unrestraint way. At the same time, the produced daughter cells too carry oncogene
and thus contain information about continuous division. Cancer is produced in this way.
Based on this trigger mechanism, two methods of treatment are proposed
a) To destroy all cancerous cells
b) To make the cancerous cell stop synthesizing oncogene
 33
LECTURE 7
THE STRUCTION AND MODELS OF MEMBRANES
Membranes surround all cells, without membranes the content of the cell would
spread out, and there would be no cell. Together with the outside membrane there exist also
intracellular membranes which subdivide the cell into compartments, each of which
performs some specific function. The thickness of the membranes is of the order of a few
nanometers, so it can’t be seen through an optical microscope. However, it can be seen
through an electronic microscope.
All types of biomembranes mainly consist of two types of compounds: lipids and
proteins, Because of their dense packing and big surface area, the total mass of lipids and
proteins in the membrane makes about the half of the dry mass of the cell. The amount of
lipids and proteins is different in different types of biomembranes. For example, in
biomembranes of bacteria causing typhus lipids make about 35%, in biomembranes of
erythrocytes it is 40%, in biomembranes of rods of retina it is 51 % in biomembranes of
nerve stems about 50-60%.
In some biomembranes there is also carbohydrates. A constituent part of
biomembranes is water, which exists in three conditions. First, it is the water bound with the
carbohydrates. Second, it is the water bound with electrically charged molecules and ions
forming a hydrate layer. And third, it is the free water. In this conditions water molecules
possess different mobility.
Lipids are esters of spirits and fatty acids. They represent a diverse group of low
molecular substances, which are solvable in organic solvents and, as a rule are badly solvable
in water and are hydrophobic. In biomembranes there exist more than 40 types of different
lipids whose relative quantities are very different in different cells and change also
depending on the cyclic phase of the cell, pathological condition of the cell, external factors,
etc.

Structure of lipids.
A lipid molecule consists of a head and tail. The head makes about 1/4 of the total
length of the molecule and tail makes about 3/4 of it. The length of the tail can reach up to
2.1 nm. The lipid head consisting of a remnant of phosphoric acid and
different radicals (choline, serine, ethanolamine, etc) is hydrophilic and
carries positive and negative charges, however its total charge is either
negative or zero. If negative, the total electric charge of the head may be
1e or 2e where e is the electron charge. Usually the tail is hydrophobic
and consists of two hydrocarbon chains − (CH) n − where n is 16-18 and
carries no electric charge. Practically water is absent there. Lipid
molecule are cone or cylinder like depending on the ratio of the square
area of the head and cross section of the tail.
Models of biomembranes
For the study of membrane structure and functions, structural and barrier properties of
lipid bilayers, damage mechanisms as well as influences of drug substances, model systems
are used by most scientists which are called artificial membranes.
 34
The latter lack the metabolic activity and don’t posses high selectivity of biological
membranes. However they model the most important biomembrane properties and make it
possible to investigate the material transport and excitability of membranes.
The most used are 3 models: monolayer, lipid bilayer and liposomes.
Monolayer
A characteristic property of lipids is their ability to self-organize. It is the result of their
amphipathic properties, that is, the hydrophilic head and hydrophobic tail, The model of
phospholipid monolayer is produced on the border of separation of two media: water/air or
water/oils. Along such border the molecules of phospholipids are arranged in such a way that
their hydrophilic heads are in the water and their hydrophobic tails are in the air or oil. If
we gradually decrease the area of the monolayer, then eventually we will obtain a
monolayer, in which the molecules are located as close to each other, as in one of the
monolayers of the real membrane bilayer.
Liposomes
The second model is the “Liposome”.
A liposome represents a biological membrane completely free
of protein molecules. They represent tiny bubbles, consisting of
bilipid membranes. Liposomes are created by radiating water and
phospholipid mixture with the help of an ultrasound. Their spherical
form corresponds to the minimum of Gibbs free energy. Thickness of
the bilipid layer is 6.5-7.5 nm. They are used as phospholipid capsules
for various drugs to introduce into organs and tissues. Liposomes are not toxic, and can be
fully assimilated by the organism. Besides, they preserve the drug from the action of
ferments. For example, insulin in a liposome capsule can be introduced orally, thus saving
diabetes patients from frequent injections. Works are being done towards treating
oncogenesis, atherosclerosis, as well as heart diseases with the help of liposome therapy.
Liposome are good for conducting experiments to investigate the influence of various
physical and chemical factors on the properties of the membranes.

Lipid bilayer
The third model of membrane represented the bilipid model which allowed investigating
many properties of real membranes directly. This model was produced in 1962 by Muller and
collaborators. In this model they filled the opening in the teflon partition separating two
water solutions, with phospholipids dissolved in heptane. After a little while, when the
solvent and surplus lipids where flown out of the teflon in the partition, a phospholipids
bilayer was formed in the opening which had a thickness of few nanometers and a diameter
of about 1mm. With the help of electrodes attached to the either side of membrane it was
possible to measure the electric resistance of membranes and electrical potentials produced
on it.
Having placed different solutions on either side of the membrane it was possible to
measure the permeability of the membrane with respect to different agents.
Biomembrane Structure
The artificial membranes didn’t correspond to the actual structure of membranes
because the membranes contain a large amount of proteins which is not present in the
models. In some membranes, the mass of proteins is more than half of the mass of
membrane. The important property of cell membranes, that is, their permeability towards
 35
hydrophilic particles also was not answered. Many suggestions for the structure of
membranes were put forward, but the most successful was the one suggested by Singers and
Nicholson in 1972.
Their model was called “fluid mosaic model”.
Again the basis of the model of the membrane
was the lipid bilayer, however the phospholipids
frame represented a two dimensional solvent in
which more or less submerged proteins floated,
With the help of this protein molecules, the
specific functions of the cell were realized which
are
(i) Permeability
(ii)Active transport through the membrane
(iii) Generation of electric potentials
Here is the approximate picture of this model
 Surface proteins
 Half submerged proteins
 Completely submerged proteins
 Proteins which make up the ion channel.
Membranes are not static and quiet structures, lipids and proteins constantly exchange their
places and partitions and move both along the membranes, which is called lateral diffusion,
and across the membranes, which is called “flip flop”. The latter diffusion (frequency is
6 ⋅ 10 6 s −1 ) is much more faster than the flip flop (frequency 10 −1 hour −1 ), in other words,
the exchange of positions of lipids, between, inside and outside of the membranes is a slow or
rare process. The mean time of such jumping transitions (about 1 hour) 1010 times exceed the
mean time of molecular transitions (transpositions) in the membrane plane.
The impeded diffusion across the membrane provides the stability and orderliness of
the membrane molecular composition, the asymmetric arrangement of lipid and protein
molecules, anisotropy, the definite orientation of protein ferments along the layer.
Experimental data obtained with the help of various physical methods have shown that
along the cell membrane the lipid composition changes, as well as the composition and
density of proteins. Under normal physiological conditions the biological membrane lipids
are found in the smectic liquid cristalline state and the average life span of settled life of its
molecule is about 10-7-10-8 sec.
The regime of functioning of the lipid bilayer is greatly influenced by its viscosity,
phase state and the mobility of phospholipid molecules. The departures of these
characteristics from the norm are the effects of various deseases.
The lipid phase of biomembranes in normal physiological conditions is in liquid
aggragative state. It has been shown that the change in its viscosity greatly influences the
vital activity of floating protein ferments. For example, oncogenesis is related to the decrease
of viscosity of the lipid phase and aging leads to increase in viscosity.
Biomembrane functions
Membranes perform three important functions :
1) barrier function, which provides an controlled, selective, active and passive
transport of substances
 36
2) Matrix function by which it plays a role of a basis for keeping protein molecules
in their definite and optimal mutual arrangement and interaction
3) Mechanical function meaning that it provides the isolation and mechanical
strength of the cell and is compartments.
Besides, biomembranes realize an energetic function too (ATP synthesis in internal
mitochondrion membranes), photosynthesis in the chloroplast membranes, generation and
transmission of biopotentials, receptor (mechanical, acoustic, olfactory, chemical,
thermoreceptive). After all, origination and transmission of biopotentials take place in
biomembranes.
In biomembranes vitally important processes take place, whose violation may lead to
numerous diseases, there are many instances when treatment is realized by directly acting on
the membrane activity.

SOME PHISICAL PROPERTIES AND PARAMETERS OF MEMBRANES

The measurement of mobility of molecules in membranes and diffusion of particles
across membranes testify that the lipid bilayer behaves like a liquid. On the other hand, it
has an orderly structure. These two facts allow to make a conclusion that the phospholipids
in the membranes in its normal condition are in the liquid crystalline state. The liquid
properties of the membranes are confirmed by the methods of electron spin resonance (ESR)
and nuclear magnetic resonance (NMR). The viscosity of the lipid layer of the membranes is
approx by two orders of magnitude greater than that of water and is about from 30 to 100
mP.s (mPS) which corresponds to the viscosity of a plant oil. The surface tension of the
membranes is by two or three orders less than that of water and is about from 0,03 to 1
mN/m.
At changing temperature a phase transition can be observed in the membrane. At
heating, the lipids are melted and at cooling they are crystallized, the phase transition is
connected with the change in energy and can be observed, for example, by the change in the
heat capacity of the membranes with changing temperature.
The conformation (structure) of molecules in the solid and liquid phases is different
which can be proved by the X-ray structure analysis. In the liquid phase the phospholipid
molecules can form cavities (kinks) in which molecules of diffusing molecules can be
embedded.
The phospholipid bilayer is likened to a capacitor with capacitance 5-13 nph per mm2.

TRANSPORT OF MOLECULES AND ATOMS THROUGH MEMBRANES

As an open thermodynamic system, cell continuously makes material exchanges
with the surrounding environment. This happens due to the permeability of the cell
membrane, and spatial transfer of mass, momentum, energy, charge and other physical
quantities is taking place. For the normal activity of cells a non-uniform distribution of a
number of molecules and ions in both sides of the membrane are necessary. The selective
permeability of the membrane from cytoplasm to the extracellular fluid and vice versa is
realized by two mechanisms: active and passive transport. They differ by the energy sources
spent for transporting.
 37
The passive transport of material is the transfer of substances from areas of higher
values of the electrochemical potential to areas of its lower values, which takes place without
a waste of the cell energy at the expense of energy of some external gradient with a number
of different mechanisms.

Passive Transport

Filtration
Osmosis

Simple Diffusion Facilitated

Diffusion
By fixed
carriers

Through Through Through By mobile

lipid bilayer lipid holes protein holes carriers

Diffusion: This is a spontaneous transfer of matter from areas of its higher

concentration to areas of its lower concentration due to the thermal motion of molecules.
Mathematically it is described by Fick’s equation
dc
j = −DgradC = −D ,
dx
where j is the flux density representing the number of particles crossing in unit time and a
unit area in perpendicular direction.
c 0 and c i are particle concentrations in the
extracellular liquid and inside the cell
respectively, and c m0 and c mi are those near
the outer and inner walls of the membrane,
which differ from c 0 and c i a little because of
different solubilities of diffusing matter in the
extracellular liquid and inside the cell. These
concentrations are related according to
c m0 c mi
= = k . k is called distribution factor.
c0 ci
If we assume that the concentration of the diffusing matter changes by the linear law, we
obtain
c −c
j = −D
dc
= − D mû mi = −
Dk
(c 0 − c i ) = −P(c 0 − c i )
dx l l
j = P(c i − c o )
Dk
P is called permeability coefficient of the membrane. So P = .
l
 38
LECTURE 8
Theorelli equation. Diffusion and Membrane potentials. Nernst potential. Rest and action
potentials.
j = P(c i − c o ) is Fick’s equation written for the diffusion of uncharged particles
through the membrane.
Now let’s Consider passive diffusion of charged particles (ions) under the action of
electric field. This mechanism of the passive diffusion obeys Ohm’s law:
dϕ
j = σE = −σ ,
dx
Where σ is the electroconductivity of the medium, E is the strength of electric field and ϕ
is its potential. Its clear that the passage of ions is possible only at the presence of a gradient
potential of electric field. On the other hand
dϕ
j = qcv = zecbE = −zecb ,
dx
where b is ion mobility, q = ze is ion charge and c is its concentration.
j dϕ
jed = = −cb
ze dx
The passive diffusion of ions under the action of electric field is called
electrodiffusion.
dϕ
jed = −cb
dx
The relationship between ion mobility b and its diffusion coefficient D is given by Einstein
Fz
formula b = D , where z is ion valence, F is the Faraday number (F=96500 C/mol), R is
RT
gas constant (R=8.31 J/mol·K) and T is absolute temperature.
If in the medium both concentration gradient and electric field gradient are present,
then for the ion flux density we get
dc Fz dϕ
j = jd + jed = −D − CD .
dx RT dx
This equation is called Nernst-Planck equation of electro diffusion or equation of
joint diffusion. Let us transform this
j=−
CD  RT dC

dϕ 
+ Fz  = −
CD d
(RT ln C + Fzϕ) = − CD dµ .
RT  C dx dx  RT dx RT dx
This is called Theorelli’s equation. Here
µ = RT ln C + Fzϕ + µ 0 ,
where µ represents the electrochemical potential, which is one of the most important
parameters describing a thermodynamic state, µ 0 is the chemical potential of the system.
Theorelli’s equation shows the moving force of the passive transport of ions is the gradient of
the electrochemical potential of the system.

Ways of the passive transport of matter through cell membrane

Simple diffusion (or electrodiffusion) across the cell membrane proceeds very slowly a
it is difficult to influence it. During evolution, for transport of ions and molecules which are
important for the vital activity of the cell several mechanisms have been developed
Fig. 1
 39

1. The lipid bilayer of the cell membrane is permeable for gases with small molecules
(oxygen, carbon dioxide), and in general, for substances which are well soluble in
the phospholipid bilayer (fatty acids, essential oils or volatile oils). This mechanism is
possible only for the permeation of non polar molecules.
2. Through lipid holes only permeation of substances with small polar molecules is
possible (for example, water).
3. Through protein holes of the membrane only molecules of insoluble substances can
permeate. The diameter of protein holes is about 6 − 10A 0 . Membrane permeability for
the transport through those holes will be given by formula
πr 2 nD
P= .
l
where n is the number of holes on a unit area, l is the length of the hole (membrane
thickness), r is the hole radius and D is the coefficient of diffusion of particles in water.
Another type of diffusion has been discovered in biomembranes called facilitated
diffusion. It proceeds with the help of carrier molecules, in that, the carriers are specialized.
For example, the carrier realizing the transport of glucose has no influence on the transport
of amino acids. The valinomicine molecule is only the carrier of potassium ions. In some
cases the facilitated diffusion is realized with the help of fixed carriers. The carriers are
aligned in some order across the cross section of the membrane, and molecules are
transmitted from one molecule to the other like in a relay race. Let us note some differences
between the facilitated diffusion and simple diffusion:
1. Diffusion with the help of carriers proceeds very fast
2. Facilitated diffusion can be saturated: at the increase of concentration of the transported
substance at one side of the membrane the flux density grows up to a certain level at which
all carrier molecule are involved.
3. When the carrier transports various substances, a competition emerges between
substances. When one of substances is transported better, this leads to a significant decrease
in the transportation of other substances.
4. There are substances, which inhibit facilitated diffusion. They produce stable bonds with
the carrier molecules and exclude them from the process.
Osmosis. Osmosis is the movement of molecules of water through the semipermeable
(permeable for the solvent (water) and not permeable for the solute) membrane from the
area of its lower concentration of the solute to the area of its higher concentration. The force
that causes this movement is called osmotic pressure. If we fill a glass tube, which closed in
on one end with a semipermeable membrane, with sugar solution and put it into a vessel
filled with water, then water will penetrate from the vessel into the tube, and the level of the
solution in the tube will be elevated. The osmotic pressure equals to the difference of
hydrostatic pressures in the tube and vessel. According to Van’t Hoff equation, osmotic
 40
pressure equals to the partial pressure of the dissolved substance. It depends on solution
concentration and temperature.
Filtration. Filtration is the passage of water through pores due to the pressure gradient. The
volumetric rate of filtration is found by Poiseuille’s formula
p − p 2 πr 4
Q= 1 = (p1 − p 2 ) ,
W 8ηl
Where r is the pore radius, other notations are familiar. Filtration play an important role in
passage of water through blood vessels.
Active transport.
Active transport is transport of substance from lower to higher value region of electro-
chemical potential.
Ussing's experiments
It was mentioned above that it is necessary to have a certain difference of ion
concentrations on both sides of cell membrane for normal bioactivity of cells. Consequently,
for maintenance of constant gradient of concentrations, the phenomenon of active transport
through cell membrane (which leads to reduction of the system's electro-chemical potential)
should also take place along with the passive transport mechanisms. Thanks to it the
gradients of electric potentials, pressures, and concentrations are kept in organism, which are
necessary for these bioprocesses. Active transport keeps the organism in a
thermodynamically non-equilibrium condition, since the thermodynamic equilibrium
destroys the organism. Ussing in 1949 proved experimentally the phenomenon of active
transport through the cell membrane using as an example the sodium ions transport.

Ion pumps, their types. Conjugate processes in ion pumps

It is evident that the active transport of ions or molecules can not take place
spontaneously, since it is related to certain energy expense. At present, it is known that the
energy source for those processes is the ATP hydrolysis reactions in cell membranes. As it
was already mentioned, a number of protein macromolecules float in cell membranes. Some
of them play a role of ingenious pumps, carrying K+ ions into the cell membrane, and Na+
ions from cytoplasm to extracellular liquid.
It was discovered that that macromolecule has two active centers, one of which can
catch Na+ ions, and the other - K+ ions. It was shown experimentally that disintegration
energy of one ATP ion is enough to evacuate 3 sodium ions from and to move in two
potassium ions into the cell. Working scheme of that molecular machine is assumed as
follows. Catching two potassium ions from the extracellular liquid and three sodium ions
from the cytoplasm, it rotates by 1800 (at the expense of ATP hydrolysis energy). Sodium
ions thus become evacuated out of the cell, and they are separated there from the protein
macromolecule. In the same way, K+ ions turn in the cell where they are also separated from
the macromolecule. After that, the protein molecule returns to its initial position and
everything is repeated again. This protein model was discovered in 1957 and is called the
sodium-potassium pump.
As Na+-K+ pump evacuates 3 ions and brings in 2 ions per cycle of work, it changes
not only the concentration of ions, but also the membrane potential (hyperpolarizes the cell
membrane).That is why the Na+-K+ pump is called electrogenic. If the supply of oxygen to
the cell is stopped, the ATP hydrolysis will not occur, and the work of this pump will stop
 41
and the membrane potential will gradually decrease. This was proved by Gerard's
experiments.
At present, two more types of ion pumps are known: Ca++ calcium pump and H proton
pump. In numerous cell processes, an important role is played by Ca++ ions. They can appear
inside the cell by different ways; however their high concentrations ( n > 10−7 mo1/ l ) are
destructive for the cell.
That is why the cell checks the Ca++ in-cell concentration and evacuates excessive
ions with the help of a special calcium pump. Therewith, the pump is electrically neutral. It
substitutes the calcium ion with two protons. For transportation of two calcium ions, the
energy released during hydrolysis of one ATP molecule is spent.
Muscle cells' calcium pumps are of a particular importance. For muscle contraction, it
is necessary to deliver Ca++ to each protein fiber and promptly remove these ions to enable
muscle relaxation. Such fast transport of Ca++ ions through the external cell membrane is not
possible. That is why the calcium pumps are densely located at internal cell membranes,
which compose a branched chain of folded caverns and pipes. During muscle relaxation, the
calcium concentration in those folds is approximately 100 times higher that its concentration
in other sites of the cell.
Proton pumps are mainly used in special abdomen cells of vertebrates. They pull H+
ions out of the cells, which is followed by negatively charged chlorine ions and owing to
this, the hydrochloric acid is formed in the abdomen. Thus, the active transport in bio-
membranes takes place with the aid of specific integral proteins called the ion pumps, which
are named also transport ATP. Ions transport with the aid of this transport ATP takes place
at the expense of chemical energy. Ion pumps carry out the various functions in organism -
feeding the cells, maintaining the salt composition in the organism's internal medium, the
regulation of osmotic processes, etc.
DIFFUSION AND MEMBRANE POTENTIALS
Diffusion potentials are produced on the boundary of two media due to the different
mobilities of ions.
Let us assume that a vessel is filled with the hydrochloric acid and divided into two
parts by a porous partition, herewith, the solution concentration in the left part is higher
than in the right part (See Figure 1). In this case, chlorine and hydrogen ions will diffuse
from the left part of the vessel to its right part, in the direction opposite to their
concentration gradient. However, since H+ mobility ( b + ) is approximately 5 times greater
than the b − mobility of Cl- ions, the diffusion of the latter will take place slower and, after
some time, the part of the solution on the right of the partition will be charged positively and
the left one negatively, correspondingly. The originated electric field will inhibit fast H+ ions
and will prompt the slow Cl- ions.
The process will continue until the ions diffusion flows become equal, that is, until
the potential difference formed between the two sides of the partition compensates
difference of mobility. Thus, for this dynamic balance state we will have equal fluxes of ions:
 42

Figure 1
dc dϕ dc dϕ
− D− ⋅ + cb − ⋅ = −D + ⋅ − cb + ⋅ (8.1)
dx dx dx dx
From which we obtain
dϕ D − − D + 1 dc RT b − − b + d
= ⋅ ⋅ = ⋅ ⋅ ln c (8.2)
dx b − + b + c dx zF b − + b + dx
Integrating equation (8.2), we obtain the following expression for diffusion potentials
difference:
RT b − − b + c
∆ϕ m = ϕ 2 − ϕ1 = ⋅ ⋅ ln 2 (8.3)
zF b − + b + c1
A particular case of difference of diffusion potentials is the membrane potential
(internal potential). We will obtain the expression for it, if the porous partition will be
replaced by the semi-permeable membrane (permeable only for one type of ions). If, for
example, the partition is impermeable for Cl- ions b − = 0 , we obtain from Eq. (8.3)
RT c
U = ϕ 2 − ϕ1 = − ⋅ ln 2 (8.4)
zF c1
This is called Nernst equation.
REST POTENTIAL
The rest potential is a stationary difference of electric potentials between internal and
external surfaces of not-excited cell membrane.

Figure 1

The rest potential of cell can be measured with the help of glass microelectrodes,
which are directly installed in the cytoplasm; the other similar electrode (the comparison
electrode) is installed in the extracellular media.
The microelectrode electronics allows to measure the membrane potentials not only
in the case of big cells, but also in the case of normal sized cells.
According to modern conceptions, the reasons for formation of rest potential is the
uneven distribution of potassium and sodium ions in cytoplasm and extracellular liquid, as
 43
well as the different permeability of the membrane to those ions. If the concentration of any
ion inside the cell ( cin ) differs from its outer concentration ( cout ) and the cell membrane is
permeable to that ion, a unidirectional flow is formed through the cell membrane.

Figure 2
It brings to violation of electric neutrality of the system (initially the solution was
electrically neutral) and formation of membrane potential, which, in its turn, obstructs ions
further transport through cell membrane. The membrane potential increase continues until a
thermodynamically balanced state is formed between the two sides of the membrane (i.e.
their electro-chemical potentials become equal). Thus,
~ + RT ln C + zFϕ = RT ln C + zFϕ + µ
µ ~
0 in in out out 0
From here, we can readily obtain the already known Nernst's equation for membrane
potential in an equilibrium state.
According to Bernstein, the rest potential is caused mainly by K+ ions transport (the
cell membrane in a rest state is permeable only for those ions, the concentration of which is
30-50 times higher inside the cell membrane than in the extracellular liquid). According to
Nernst equation this means that
RT [K + ]in
U rest = ϕin − ϕout = − ln (8.5)
zF [K + ]out
It is easily obtainable also, that for the equilibrium membrane, for the potential origination
(60-90mV) only a negligible change of ion additional concentration (only small quantity of
them should pass) is needed. The rest potential determined by expression (8.5) is in a good
correspondence with the experimentally determined values of Vres for almost all known cells.
However, in some cases the more precise measurements had discovered some
difference between experimental results and those obtained with the aid of Eq. (8.5). This is
caused by the fact that in the rest state the membrane, to some extent, is permeable also for
other types of ions. Based on this, Goldman suggested the so called stationary model for
origination of the rest potential, according to which the value of membrane potential is
determined from the condition of total flux absence for ions through the cell membrane for
all types of ions. That is, for example, it is assumed that the inflow to cytoplasm is equal to
the outflow from it. As far as K+ , Na+ and Cl+ ions are present mainly in the extracellular and
intra-cell solutions, the condition of flow vanishing is the following:
j Na + + jK + − jCl− = 0 (8.6)
If this condition is met, an expression is obtained (Goldman-Hodgkin-Katz) for the
membrane potential that is in a better agreement with the experimental results. In resting
membrane, permeabilities of different ions relate as
( PK , : PNa : PCl = 1 : 0,04 : 0,45 ).
 44
ACTION POTENTIAL
In living organisms, the information is transformed by the aid of electric nerve pulses
(action potentials) from receptors to brain neurons and from those neurons to muscle tissues.
Living organisms represent by themselves a fully electrified system.
Some 200 years ago Galvani, based on his electro-physiological experiments, showed
that the muscle contractions take place under the influence of electric pulses and that any
living system is a source of electric pulses (it is to be noted that there were no other
electricity sources known at that time). However, the electric nature of nerve pulses was
proved finally only in the middle of XX century by Hodgkin and Huxley, for which they
were awarded the Nobel Prize in 1963.
Electric pulse that is formed in cell membrane due to the change of its ion
permeability under the influence of an excitation wave propagating along the nerve fibers
and muscles is called the action potential.
In nerve and muscle cells, the duration of this process is approximately equal to 1
msec . The characteristic features of the action potential are:

1. The existence of threshold value of depolarizing excitation impulse,

2. There is a time period of cell membrane refractability. That is, the site is not excitable 1-3
ms after the first excitation. The rule "everything or nothing" is acting, i.e., when an exciting
potential exceeds some threshold value U thresh , an action potential is developed, the
amplitude of which is independent on the amplitude of the exciting potential. And for
U < U thresh the action potential cannot be formed. Hodgkin and Huxley; experiments
showed unambiguously that the formation of action potential is a result of the sharp increase
of the cell membrane permeability for sodium ions (about 500 times) during its excitation.
Permeabilities now relate as
PK : PNa : PCl = 1 : 20 : 0,45
 45
Lecture 9.
The ELECTRIC ACTIVITY of ORGANS

The functioning of living cells is accompanied by occurrence of transmembrane

electric potentials. Cells, forming a complete organ, develop a complex picture of electric
activity of the organ. This picture is determined by the electric activity of separate cells,
interaction between them, by structure of the organ, processes of regulation in it and by a
series of other reasons.
Electric activity to a large degree reflects the functional state of cells, tissues and
organs. Registration and analysis of electric activity allows one to carry out biophysical,
medical and biologic researches to study the work of the organ and to carry out clinical
diagnostics.

The external electric fields of organs.

A principle of the equivalent generator.
Going from the cellular to the organ level (the next level of organization of living
systems) the problem arises of the description of distribution of electric potentials on the
surface of this organ as a result of consecutive excitation of separate cells. During the process
of living activity the state of the organ and, consequently, its electric activity vary constantly.
First, it is caused by the propagation of waves of excitation in nervous and muscular fibers.
For scientific purposes, it is possible to measure the potential difference directly on the
surface or in internal structures of the investigated organ (heart, brain etc.). However, in
clinical practice such a direct measurement of potential difference on the organ is difficult.
Even in cases when it is possible, temporal changes represent a difficult problem.
Thus, to estimate the functional state of an organ by its electric activity, the principle
of the equivalent generator is used, that is, the organ under investigation, consisting of a
system of cells exciting at various moments of time, is represented by a model of the single
equivalent generator. It is assumed that this equivalent generator is situated inside the
organism and creates an electric field on the surface of an organ, this field changing in
accordance of the changes of the electric activity of organ under investigation.
The term "equivalent" means that the distribution of potentials on the surface of the
body and their changing in time generated by the organ should be close to that produced by
the hypothetical (imaginable) generator. Thus, for example, in the Einthoven’s theory, the
heart, the cells of which are excited in a complex sequence, is represented by a current
dipole (the equivalent generator). It is also assumed that change of potentials of the electric
field on the surface of the chest caused by the change of the electric moment of the dipole is
the same as for the working heart.
The method of investigation of work of organs or tissues based on time registration of
electric field potentials on surfaces of a body is called the electrography. Two electrodes
applied to different points of the surface of the body register a potential difference varying in
time. Temporal dependence of change of this potential difference is called electrogram.
The name of electrogram points to the organ (or tissues) whose function results in an
occurrence of registered changes of a potential difference for:

• heart – ECG (EKG) (electrocardiogram),

• retinas of an eye - ERG (electroretinogram),
 46
• brain - EEG (electroencephalogram),
• muscles - EMG (electromyogram),
In electrography there are two fundamental problems which arise:
1) The direct problem - the calculation of electric potential distribution on a
given surface of an organ under the given characteristics of the equivalent generator;
2) The inverse problem, the definition of characteristics of the equivalent
generator (investigated organ) by measuring potentials on the surface of the organ.
The inverse problem is a problem of clinical diagnostics: measuring and registering,
for example, EKG (or EEG) may estimate the functional state of the heart (or brain).
The Physical Basis of Electrocardiography
At present, the study of electric activity of the heart, Electrocardiography, is most the
widely used in medical practice.
The experimental data show that process of propagation of excitation along various
parts of the heart is complicated. Propagation speeds of excitation vary in heart by direction
and value. In walls of auricles the excitation is propagated with the speed 30 - 80 cm/s, in
atria ventricular node it is retarded up to 2 - 5 cm/s, in His bundle speed is maximal, reaching
100 - 140 cm /s.
As a result, the wavelengths of excitation

λ = RV ,
where R is the refractory period, will also differ in various parts of system of excitation
propagation. Thus, in auricles it is equal to λ ≈ 12cm , in atria ventricular node λ ≈ 0, 6cm , in
legs of His bundle λ = 30cm .
The full description of the electric state of the heart, the mathematical description of
distribution of membrane potentials over the whole volume of the heart in each cell and the
description of time changing of these potentials is impossible.
Therefore, in accordance with the principle of equivalent generator, the heart is replaced
by the equivalent current generator, electric field of which is similar by its properties to the
electric field created by heart
To calculate potentials of electric field created by the current generator in a
homogeneous conducting media the heart is represented as current electric dipole, that is, as
consisting of positive and negative poles (source and run-off of electric currents), located on
small distance l from each other. The main parameter of current dipole is dipole momentum
 
d = Il .

The vector d is directed from "-" to "+", from a run-off to a source, that is, along the
direction of the electric current in the internal circuit of the current generator. If it is
possible to neglect l with respect to distances under the given experimental conditions, the
dipole is called the point dipole.
To calculate the potentials of the electric field of a current dipole, at first the field of
unipole, one of the poles of dipole, is considered separately.
The potential of an electric field of unipole (Fig 1) can be calculated on the basis of
the Ohm's law written in the differential form (eq.9.1).
 47

Figure 1 To the calculation of the electric field potential of unipole: a) source; b) run-off
According to this law the density of an electric current j , that is, an electric current
through the unit area j = I / S :
1 dϕ
j= − ⋅ (9.1)
ρ dr
where ρ is the specific resistance of media in which the current generator is working, ϕ
is the potential of the electric field, r is distance from a unipole. j is called current density. It
A
is measured in 2 .
m
On the other hand, by definition
I
j= (9.2)
4π r 2
Here I is the current generated by the current generator, and 4π r 2 is the area of sphere
of radius r through which current I flows. From (9.1) and (9.2) is follows:

I 1 dϕ
=− ⋅
4π r 2
ρ dr
From here, we have

I
dϕ = − ⋅ ρ dr (9.3)
4π r 2
Assuming that the conducting media is boundless and infinite in comparison with the size
of a dipole and integrating Eq (9.3) from ∞ to r , it is possible to find potential ϕ a of point A ,

placed from unipole on distance r :

ρ I dr ρI  1 ρI 1 ρI
r r r r r
I
ϕ A =∫ dϕ =− ∫ ⋅ ρ ⋅ dr =− ∫ 2 =−  −  =   =
∞ ∞
4π r 2
4π ∞ r 4π  r  ∞ 4π  r  ∞ 4π r

ρI
ϕA =
4π r
This is the final expression for potential of an electric field of positive unipole
(source). In this case the integration is carried out from ∞ to r ,the potential decreases along
the direction of a current, ϕ = 0 when r → ∞ . In the same manner, for field of negative
unipole (run-off) the potential is equal to
ρI
ϕA = −
4π r
For an electric field of a dipole (see Fig. 2) the potential ϕ A will be the sum of
potentials of the electric fields created by unipoles of both signs + (source) and - (run-off):
 48
ρI ρ I ρ I r − r1
ϕA = − = ⋅ (9.4)
4π r1 4π r 4π rr1

Where r is the distance from a positive pole, and r1 from a negative pole of a dipole,
correspondingly.

Figure 2 The calculation of potential of an electric field of a

dipole
If l << r (a point dipole), it is possible to approximate
(Fig. 2)

r ⋅ r1 ≈ r 2 , and r − r1 ≈ l cos θ
(9.5)


where θ is the angle between vector d and direction from the to
point A .
Substituting Eq. (9.5) in Eq. (9.4), we obtain
ρIl ρd ρ
ϕA = cos θ = cos θ = k 1d cos θ where d = Il , and k 1 = ..
4πr 2 4πr 2 4πr 2

Figure 3 Calculation of a potential

difference of an
electric field of dipole.
Difference of potentials of two points
of the field created current dipole (Fig. 3):

∆ϕ = ϕ A − ϕ B = k1d cos θ A − k1d cos θ B = k1d(cos θ A − cos θ B ) (9.6)

if points A and B are on the same distance r from a dipole. According to trigonometry
formulas, it is possible to obtain that

∆ϕ = ϕ A − ϕ B = 2kd sin β cos α . (9.7)

Introducing coefficient of proportionality
= k 2k1 sin β (9.8)
one may write
= ∆ϕ kd cos
= α kd AB (9.9)

where d AB is the projection of a vector d on straight line АВ.
Thus, the potential difference of two points of a field of the point electric dipole,
located on the same distance from a dipole, is proportional to a projection of dipole moment
on a straight line on which these points lay.
 49
Investigating changes of the potential difference on the surface of the human body, it
is possible to predetermine the projections of the dipole moment of the heart, hence, the
biopotentials of the heart.
This idea is placed in the basis of Einthoven’s model, the Dutch scientist, the founder
of electrocardiography, the Nobel Prize winner of 1924.
The basic postulates of this model are the following:
1. Electric field of heart is represented as an electric field of point current dipole with

dipole moment D called an integrated electric vector of heart (IEVH) (is sum of dipoles of
 
different parts of heart: ( D = ∑ d i ).
2. IEVH is situated in homogeneous isotropic infinite (boundless) conducting media
which represent the organism tissues.

3. The integrated electric vector of heart D varies in size and direction. Its beginning
(tail) is stationary and situated in atrioventricular node, and the end (head) describes a
complex spatial curve, which projection on the frontal plane forms three loops over one
cycle of activity (in norm); P, QRS and T.
Obviously, at different points of the surface of the chest at the given moment of time
there will be different electric potentials in size and sign. At next moment of time the
distribution of these potentials on the surface of the body will change.
Vectorcardiography
This is a technique, allowing to see the IEVH vector in space by registering the

projections of the complex spatial curve described by the end of vector D on frontal, saggital
and horizontal planes.
For obtaining the vectorcardiogramme the electronic oscillograph is used. On the screen
of an oscillograph there is an addition of two mutually perpendicular fluctuations (Lissagou
pictures).
Clinical Electrocardiogram (ECG)
The heart pumps blood when the muscle cells of the heart contract, generating action
potential. The potential creates electrical currents that spread from the heart throughout the
body. The spreading of electrical currents creates differences in electrical potential between
various locations in the body, and these potentials can be detected and recorded through
surface electrodes attached to the skin. The electrocardiogram (ECG or EKG) is a graphic
recording of the rhythmic time-variant voltages produced due to electrical depolarization
and repolarization of the heart muscle (myocardium) during the cardiac cycle. The P-wave,
P-R interval, QRS peak, S-T segment and the T-wave reflect the rhythmic electrical
depolarization and repolarization of the myocardium associated with the contributions of the
atria and ventricles, (Fig.4.).

Figure 4. Normal ECG record.

The component produced by the atrial activation is
P-wave.
The component produced by ventricular activation is
QRS-complex.
The component produced by recovery is T-wave.
 50

To record an electrocardiogram, electrodes are fixed to the body of the patient. The wave-
form of the ECG is very dependent on the placement of the electrodes. The ECG machine
uses the patient's right leg as the common electrode. The bipolar limb leads (I, II and III)
form the Eindhoven triangle (Fig. 5).
RA = Right arm; LA = Left arm RL = Right leg; LL = Left leg Right leg(RL) is grounded.
Figure 5. A five-electrode arrangement/or ECG recording.
Both time and amplitude analyses are to be taken into
account in interpretation RA = Right arm; LA : Left arm; LL = Left
leg
Through the ECG analysis, conditions associated with the
heart and various diseases can be diagnosed. Some of these are—
heart arrhythmia, myocardial infarction, ectopic beats,
hypertension, congenital heart diseases, muscle destruction and ischemia, pulmonary
emphysema and other cardiac syndromes. Non-rhythmic cycles (bradycardia or tachycardia)
symptoms of arrhythmia of ECG profiles. If P-R interval is > 0.2 sec, it could be due to
blockage atrioventrical (AV) node (obstruction of the spread of excitation from atria to
ventricles). The longer duration of QRS complex (>0.1s) is indicative of bundle block. In
coronary insufficiency (deficient blood circulation in the coronary arteries), the S-T interval
is shortened and the T-wave is some times inverted. As changes in T-wave can result from
even the slightest) change in the period of depolarization of only one position of the heart,
the T-wave is one of most important indicators in the ECG of the cardiovascular
abnormalities.
While ECG provides useful information in the case of arrhythmia and myocardial
infarctions it cannot provide information on disorders involving the heart valves. These can
be diagnosed from angiography and echocardiography.
The research method of electric activity
of brain –the electroencephlography
Registration and analyses of the time dependences of differences of potentials created
by the brain on the surface of the head may be used for diagnostics of various kinds of
pathologies of the nervous system: traumas, epilepsy, mental disorders, and insomnia.
Electroencephlography is used in medicine for defining the area of the tumour of the
brain, for an estimation of the functional state of the brain before introduction of some
medicine.
Registered potential differences are 100 times weaker than in ECG: 0,1 - 5 mV in ECG and
0,001 - 0,05 mV in EEG. Therefore, more powerful amplifiers of biopotentials must be used.
Electroencephalography is technique for recording and interpreting the electrical activity
of the brain. The nerve cells of the brain generate electrical impulses that fluctuate
rhythmically in distinct patterns. In 1929 Hans Berger of Germany developed an
electroencephalograph, an instrument that measures and records these brain wave patterns.
The recording produced by such an instrument is called an electroencephalogram,
commonly abbreviated EEG. To make an EEG, electrodes are placed in pairs on the scalp.
Each pair of electrodes transmits a signal to one of several recording channels of the
electroencephalograph. This signal consists of the difference in the voltage between the pair.
The rhythmic fluctuation of this potential difference is shown as peaks and troughs on a line
 51
graph by the recording channel. The EEG of a normal adult in a fully conscious but relaxed
state is made up of regularly recurring oscillating waves known as alpha, beta and gamma
waves.
The frequency of α wave is in the 8-13 Hz range,
The frequency of β wave is in the 14-35 Hz range and
The frequency of γ wave is in the 36-70 Hz range
When a person is excited or startled, the alpha waves are replaced by low-voltage, rapid,
irregular waves. During sleep, the brain waves become extremely slow. Such is also the case
when a person is in a deep coma. In these cases delta and theta waves are prevalent. Other
abnormal conditions are associated with particular EEG patterns. Irregular slow delta waves
arise, for example, from the vicinity of a localized area of brain damage.
The frequency of δ wave is in the 0.3-3 Hz range and
The frequency of θ wave is in the 4-7 Hz range and
Electroencephalography provides a means of studying how the brain works and of tracing
connections between one part of the central nervous system and another. Its effectiveness as
a research tool, however, is limited because it records only a small sample of electrical
activity from the surface of the brain. Many of the more complex functions of the brain, such
as those that underlie emotions and thought, cannot be related closely to EEG patterns.
Electroencephalography has proved more useful as a diagnostic aid in cases of serious head
injuries, brain tumors, cerebral infections, epilepsy, and various degenerative diseases of the
nervous system.

Lecture 11
Biophysics of Muscle Contraction
The whole living activity of people and animals is inseparably connected with
mechanical motion realized by muscles.
All body movements, breathing, blood circulation, functioning of the gastrointestinal
tract, automatism of the heart contractions are provided by muscle activity, which is
stipulated by the special protein contractile complex- actomyosin, present in it.
Modern experimental data testify that the contractile elements have a tremendous
role in the microprocesses, in particular, in the active transport across the membranes, in the
continuous movements (oscillating, cycling, streaming) of the cytoplasm, which are very
important for the metabolism in the cells.
The above brief presentation certainly reflects the great importance of investigation
of the mechanism of muscle functioning in diagnostic problems, for example, the disorders
in the functioning of the heart and lung muscles can lead to pathologies, and the halting of
their functioning results in the lethal outcome. The direct conversion of chemical energy
into mechanical energy avoiding the intermediate phases of the transition into heat or
electric energies might solve the problem of creation of a new type of heat engines.
By their mechanical properties, muscles belong to such substances which possess
elasticity (stretchablility and elasticity). Such substances are called elastomers.
If the muscle is subjected to the action of an external mechanical force, then
according to Hooke’s law for elastic (small) deformations we have
 52
S
F = k∆l , where ∆l = l − l 0 is the absolute deformation and k = E with E being
l0
∆l
Young’s module. Introducing relative deformation or strain = ε ,Hooke’s law can be
l0
represented in the form
σ = Eε .
F
Here σ is the mechanical stress = σ .
S
By its properties muscle resembles rubber. Like in the latter, in the muscle too at
much stretching local crystallization is observed. This has been proved by X-ray structural
analysis. As a result, a crystallization heat is released, and the muscle temperature increases.

Structure of transversal-striated muscles. The model of sliding filaments

The muscle tissue represents a system of muscle cells (fibers), extracellular substances
(collagen, elastin, etc), a dense net of nerve threads and blood vessels.

By their structure muscles are divided into smooth muscles (intestines, muscles of the
blood vessels), transverse striated muscles (skeletal muscle, cardiac muscle).
Independent of the structure, muscles possess mechanical properties, the same
activation mechanism, as well as have almost the same chemical composition.
Mechanical properties of muscles resemble that of polymers. That is, they have both
viscous and elastic properties. The elastic properties are modeled by the elastic element, a
spring (Fig. a) and the viscous ones are modeled by a viscous element, a cylinder filled with a
viscous liquid, in which a piston with holes in it can move (bumper) (Fig. b). Actual bodies
are modeled by different combinations of these elements.

a) Elastic element b) viscous element

Relaxation of stress in the smooth muscles corresponds to the Maxwell model

combining elastic and viscous properties. In the Maxwell model the elastic and viscous
elements are connected in series

For this reason the smooth muscles are considerably stretched without much stress,
which helps the hollow organs expand, for example the bladder can expand in quite a wide
limits.

E
− t
σ = σ0 ⋅e η
 53

σ
ε= t
η

In actual polymers the joint viscous elastic deformation arises just after the loading,
therefore this corresponds to Kelvin Foicht model.

The analogue is
car bumper

As a result, deformation first increases by the exponential law and when the load is
removed (σ = 0 ) , deformation decreases exponentially.

σ  
E
− t
ε= 1− e η 
E  


The mechanical behavior of skeletal muscles corresponds to the following model of

strong viscous-elastic deformation

Mechanism of muscle contraction

The skeletal muscle of vertebrates consists of a strand of a few ten thousands of
parallel fibres of diameter 10-100 mcm which are surrounded by a common membrane. At
each muscle fibre a nerve ending is attached through which it receives nerve impulses and
 54
can contract. Each ending of the muscle represents a tendon, which bears the stress of
muscle contraction.
The muscle fibre
containes 1000-2000 parallel
muscle fibrils, myofibrils,
with about 1 mcm diameter.

The strand of
myofibrils is enclosed in a
membrane:
plasmalemma, which is
made up of two layers:
protein and lipid, having
10 nm total thickness
and is polarized. The
membrane potential is
100 mV.
From outside the
plasmalemma is covered by a thin layer of collagen threads, which possess elastic properties.
In the muscle fiber there are many nuclei (arranged near the plasmalemma) and a
great number of mitochondrions, which are centers
of production of high-energy compounds, first of all
ATP. From here the high-energy compounds are
transferred through sarcoplasm to fibrils.

Myofibrils are separated into

A zone, which is anisotropic and gives
birefrigence
I zone, which is isotropic
Z lines
Between two adjacent Z lines the elementary
contractile unit, sarcomere is located.
 55

Sarcomere is a system of thick and thin myofilaments. The thickness of the thick
filament is 12 nm and its length is 1.5 mcm. It is made up of protein myosin.
The thickness of the thin filament is 8 nm and its length is 1 mcm. It is made up of
protein actin and by one end is connected to the Z line.
The actin filament consists of two threads of 5 nm thickness twisted around each
other.
This structure resembles a bead composed of two threads with 14 beads in each turn.
In the actin chain at distances about 40 nm troponin molecules are inserted and the
chain is enveloped by tropomyosin threads.
During muscle contraction the thin myofilaments shift between the thick
myofilaments. A sliding of myofilaments takes place without change in their lengths.
This process is caused by the action of special outgrowths of myosin, myosin heads.
These heads (tranverse bridges) with their active centers are located on the actin.
Heads are away from the thick filament by 14 nm periodicity from each other.

When myofibrils are relaxed the tropomyosin molecules block the attachment of
bridges to actin helix.
Ca+ ions activate the bridges and open their attachment areas with actin. As a result,
myosin heads attach to actin filaments, ATP molecules break up and myosin head
conformation changes.
Their heads bend inside the sarcomere and as a result sliding force is created, which
moves actin relative to the myosin filament and is directed to the center of sarcomere. The
muscle contracts.
At the end of the activation, the bridge is lifted, and sarcomere returns to its initial
state.
Each cycle of closing and lifting of the bridge is accompanied by the breaking up of
one ATP molecule.
Summarizing, we can state that the actin-myosin complex represent a mechano-
chemical converter of ATP energy.
 56
The sliding of sarcomere filaments was discovered by English scientist Huxley who
suggested the model of sliding filaments.
The model has been confirmed by experimental methods and represents an
established fact, which serves as a basis for all contemporary theories of muscle contraction.
The experimental data is the result of electronic microscope, X-ray structural analysis
and diffraction of synchrotron radiation methods.
Main principles of the model of sliding filaments
1. During contraction, lengts of actin and myosin filaments don’t change
2. The change in the length of sarcomere is the result of longitudinal relative motion
of actin and myosin filaments
3. The transverse bridges outgrowing from myosin can attach to complementary
centers of the actin molecule
4. Bridges attach to the actin filament not simultaneously
5. The closed bridges are subjected to a structurally transition at which the necessary
effort is produced, and then their disconnection follows
6. The muscle contraction and relaxation represents the increase and the subsequent
decrease in the number of bridges performing the closing-lifting cycle.
7. Each cycle is provided by hydrolysis of one ATP molecule
8. Bridges function independently

Hill Euation. Power of a single contractin

The rate of contraction depending on load P is one of important points in studying mussle
since it reveals the regularities in muscle contraction and its energetics. It was investigated in
detail by Hill for different regimes of contraction and is represented in Fig. 1. He also
suggested an empirical formula describing that graph:
b(P0 − P)
V(P) =
P+a

where P0 is the maximum isometric tension developed by the muscle or the maximum load
maintained by the muscle without stretching, b is a constant having dimension of velocity
and a is a constant having dimension of force.
From this equation it follows that the maximum velocity occurs at P=0,
b
Vmax = P0 .
a
At P= P0 we obtain V=0, meaning there is no contraction.
The work done by the muscle at a single contraction by amount Δl is equal
A=P Δl
This dependence obviously is nonlinear, because V=f(P). However at the initial stage of
contraction this nonlinear dependence can be ignored and held V=const. Then
 57
dA
∆l = V∆t and for the power W= we will have
dt
W=PV.
Putting here Formulas (2) and (3) we obtain the dependence of power on developed force P:
b(P0 − P)
W = PV = ⋅P.
P+a

Young (elasticity) Modulus for some substances

Material Young Modulus in P

Elastin 6 · 105

Collagen 109

Bone 1010

Rubber 106

Oak 1010

Steel 2 · 1010

20% of muscle proteins is collagen

Elastin is the elastic protein of artery walls
 58

Lecture 12
Thermal Radiation
Emission of electromagnetic waves by substances takes place due to inter-
atomic and inter-molecular processes. The source of energy and the typy of emission
can be different: TV screen, daylight lamp (fluorescent lamp) incandescent lamp,
rotten wood,etc.
From the whole diversity of electromagnetic radiation one can separate the one
(visible or invisible to human eye) which relates to all bodies. It is the radiation of
heated bodies or thermal radiation. It exists at all temperatures greater than 0oK and
thus itted by all bodies. Depending on body temperature, the intensity of radiation
and spectral composition changes and thereby not that in all cases is it perceived by
eye as anillumination.

Characteristics of thermal radiation: absolutely black body

dE
The mean power of radiation in time is the flux of radiation: φ = . In SI it is
dt
expressed in watts (W).
The flux of radiation emitted from square area of 1 m2 of the body surface is the
energetic luminosity R. It is measured in W/m2. Hot bodies emit electromagnetic
waves of various wavelengths. Let us separate a narrow interval of wavelengths from
λ to λ+dλ. The energetic luminosity corresponding to that interval is proportional to
the width of the interval: dRλ∼dλ, thus
dRλ=rλdλ (1)
where rλ is the spectral density of energetic luminosity representing the ratio of the
energetic luminosity of that narrow interval with the width of that interval and is
measured in W/m3.
The dependence of the spectral density of energetic luminosity on wavelength
represents the radiation spectrum of the body. Integrating (1), for the energetic
luminosity of the body we obtain the expression
∞
R e = ∫ rλ dλ . (2)
0
The limits of integration are taken from 0 to ∞ to account for all wavelengths.
The ability of body to absorb energy is described by the coefficient of absorption
which represents the ratio of the absorbed flux with the incident flux of radiation
φ
α = absorb. (3)
φ incid.
Since the coefficient of absorption depends on the wavelength, then for the
monochromatic coefficient of absorption (3) we can write
φ (λ )
α λ = absorb. (4)
φ incid. (λ)
 59
From (3) it follows that the coefficient of absorption can take values
from 0 to 1. Especialy well is the radiation absorbed by black bodies
(black paper, textile, …) and badly by white and smooth/unruffled
surfaces.
The body whose coefficient of absorption equals to unity for all
frequencies is called a blackbody. It absorbs all radiations incident on
it. There are no absolute blackbodies in the nature. This is an abstract
physical concept. For example, a black body is a non-transparent camera having a
small hole. A beam of light once inside, is reflected many times by the walls of the
camera and eventually is absorbed. The body whose absorption coefficient is less than
unity and doesn’t depend on wavelength is clled a grey body. For example, often
human body, whose absorption coefficient is about 0.9 in the IR region og spectrum,
is considered as grey.

Kirchhoff law
There is a certain relationship between spectral density of energetic luminosity
and monochromatic coefficient of absorption of a body, which can be explained on
the following example.
There are two different bodies at a thermodynamical equilibrium in a closed
adiabatic shell. In this case their temperatures are the same. Since body temperatures
do not change, each of them emits and absorbs the same energy. Radiation spectrum
of each of the bodies must coincide with with the spectrum of electromagnetic waves
absorbed by it. Otherwise the thermodynamical equilibrium would be broken. It
means that when one of the bodies emits some wave more, for example, red
one, then it must absorb it (red) more. The quantitative relationship between
emmision and absorption was established by Kirchhoff in 1859. The ratio of
spectral density of energetic luminosity with monochromatic coefficient of absorption
at constant temperature is the same for all bodies including blackbodies (Kirchhoff’s
law)
r r ε
( λ )1 = ( λ ) 2 = ... = λ
αλ αλ 1
Where ελ is the blackbody spectral density of energetic luminosity. Kirchhoff’s
law can be written also in the following simple way
rλ
= ελ ,
αλ
from which it follows rλ = α λ ε λ .
Since αλ<1, then as it follows from the above equation, spectral density of
energetic luminosity of all bodies is less than the spectral density of energetic
luminosity of the blackbody. The blacbody is the most intense source of thermal
radiation (at the given temperature).
From the last expression it can be seen that when a body doesn’t absorb an
emission (αλ=0), then it also doesn’t emit it (rλ=0). Using Kirchhoff’s law and learning
 60
the radiation spectrum of the blackbody ελ=f(λ) from experiment and dependence of
the monochromatic coefficient of absorption on the wavelength αλ= f(λ), one can find
the radiation spectrum of the body rλ=f(λ).

Laws of the blackbody radiation (Stefan-Boltzmann and Wien laws)

The radiation of the blackbody has a continuous spectrum. The spectra of radiation at
different temperatures have the following shapes

From this experimental curves one can make a number of conclusions

1. There exists a maximum for the energetic luminosity, which shifts
towards the shorter wavelengths when temperature increases
2. On the basis of the graph onecan find the energetic luminosity of the
blackbody Re as the square area of the figure bounded by the graph and
the abscissa axis or
∞
R e = ∫ ε λ dλ (5)
0
3. From the graph it can be seen that the energetic luminosity increases with
the heating up of the blackbody.
The dependence of ελ=f(λ) for the blackbodies was derived by Planck theoretically in
1900.
In classical physics the emission and absorption of radiation by a body is considered as
a continuous process. Planck developed the hypothesis the blackbody radiates and
absorbs energy not continuously but rather by certain portions, quanta.
Representing the body as a system of oscillators (a physical system making
oscillations), whose energy was E=hν, where ν was quantum frequency, Planck
derived the formulae
2πhc 2 1 2πυ 2 hυ
ελ = ⋅ or ε λ = ⋅ (6)
λ5 e hc KTλ
−1 c2 e hυ / KT − 1
Here h=6.62⋅10-34 J·s is the Planck constant, c=3⋅108 m/s is the speed of light in vacuum
and K=1.38⋅10-23 J/deg·mol is the Boltzmann constant.
 61
From equation (5) taking into account equation (6) the energetic luminosity of the
black body can be found
∞ dλ
R e = 2πhc 2 ∫ . (7)
5 hc / KTλ
0 λ [e − 1]
By making a substitution of variable we finally obtain
R e = σT 4 (Stefan-Boltzmann law) (8)
2π 5 K 4
Here σ = ≅ 5.66 ⋅ 10 − 8 W/m2K4 is the Stefan-Boltzmann constant.
3 2
15h c
Energetic luminosity of the blackbody is proportional to the fourth power of
its absolute temperature.
For a grey body
R e = ασT 4 (8)
Stefan-Boltzmann law can be quantitaively illustrated for different bodies
(stove, electric heater, etc), when they are heated, more intense radiation is
realized.
dε λ
ελ possesses an extremum when equation =0 (9)
dλ
is fulfiled. From here Wien displacement law can be derived.
Where λmax is the wavelength which maximum energetic
luminosity comes upon. b=0.289⋅10-2 m is Wien constant. This law
holds for the grey body too.
With the help of Stefan-Boltzmann and Wien laws allow finding
the body temperature by measuring body temperature (optical pyrometry).

Solar radiation. Application of sources of thermal radiation for medical aims

The most powerful source of thermal radiation, which makes life on the earth
possible, is the sun. The flux of solar radiation which is incident on the frontier of the
earth atmosphere is 1350 W/m2. This quantity is called solar constant. Depending on
the altitude of the sun relative to the horizon the distance sun beams cover in the
atmosphere changes in quite a wide limits.
Even in the most favorable
conditions the flux of solar
radiation flux is 1120 W/m2.
The maximum of the spectrum
corresoponds to λmax=470 nm,
which allows with the help of
Wien law to determine the
surface temperature of the sun,
which makes about 6100oK.
The intensity of the direct solar
radiation is measured by an
 62
actinometer. Its principle of operation is based on the heating of the surface of a
blackened body taking place under the action of the solar radiation.
Dosated solar radiation is applied as a solar treatment (heliotherapy) as well
as means of organism training. For treatment purposes sources artificial thermal
radiation are used too, incandescent lamps.

Heat emission of living organism. Idea about thermography.

Due to thermoregulation, human body has a definite temperature, which is

mostly regulated by the heat exchange of the organism with the surrounding
medium. The heat exchange takes place by direct heat transfer, convection,
vaporization radiation (absorption).
To account for these losses we make two basic admissions
1. The emitting bodies (human skin, clothing textile) we take as grey bodies. This
allows to apply formula Re=δT4
2. Stefan-Boltzmann law we apply for a non uniform radiation, which in
particular refers to the human body radiation. From the square area of S of the
open parts of its body a man radiates some power P1,which is equal to SδT14
and the absorbed power is P0=SδT04.
Thus in interacting with the surrounding bodies the energy it loses will be
P=P1-P0=Sδ( T14- T04),
Let us put t0=180 and t1=310 , we will obtain
P=1,5⋅5,7⋅10-8(3064-2914)J/s≈122J/s.
Because of the strong dependence of the energetic luminosity on temperature,
even a sleight increase in the temperature leads to such an increase in the emitted
power that will easily be registered by devices. To explain it quantitatively, let us
differentiate Re=δT4. We get dR=4δT3dT. Dividing the last two expressions we get
dR 4dT
=
Re T
This infers that the relative change in the energetic luminosity is four times greater
than the relative change in the temperature of the body surface. So, if the human
body surface temperature changes by 30C, that is by 1%, its energetic luminosity
changes by 4%. Therefore the registration of radiation from different parts of the
body and determination of their temperature represents a diagnostic method, which
is called thermography and it has wide applications in clinical practice.
Thermography is exclusively unharmful and in perspective can become a mass
method of preventive diagnostics.

Influence of Infrared an UV radiations on living organisms and their application in

medicine
 63
Together with the visible radiation 400-760 nm), there exist also invisible
radiations.
The electromagnetic radiation which occupies the spectral region of the
boundary of red light (λ>760 nm) and short wave radio radiation (λ=1-2 nm) is called
infrared radiation. The electromagnetic radiation which lies below the violet limit of
the visible light (λ<400 nm) and in the longwave X-ray radiation (λ=10 nm) is called
ultraviolet radiation. They have been discovered with the help of sensitive photocells
(electrooptical transducers) or sensitive thermocouple, at the basis of which lies the
thermal action.
Infrared radiation is emitted all hot bodies (lamp, stove, heaters). The
therapeutic application of the infrared radiation is based on its thermal action.
Infrared radiation penetrates in body to a depth of some 20 mm and so the surface
layers are heated most.
The treatment and preventive methods which use radiations of infrared (1
mcm to 760 nm), visible and ultraviolet (380 nm to 200 nm) wavelengths is called
phototherapy.
With the increase of wavelength the ultraviolet radiation is used for
prevevntive (antirachitic), therapeutic and anticontagious (bactericidal action) aims.
The ultraviolet radiation has the property of penetrating into tissues relatively not
deeply (skin layer). Infrared and visible radiations penetrate the tissues more deply. In
general, optical radiation can have both thermal and chemical influence, but infrared
radiation leaves mostly thermal influence and ultraviolet radiation chemical
influence.

Lecture 10
Biophysics of Blood Circulation
The cardio-vascular system is considered to be a close system consisting of millions of vessels
of different diameters from 10-4cm to 2 cm.
Schematically the cardio-vascular system can be represented in this way

HEART

VEINS AORTA

VENULES ARTERIES

CAPILARIES

The cardio-vascular system provides the blood circulation in the closed vessel system.
The permanent blood circulation allows to deliver to all cells substances that are necessary
normal existence and remove the waste products from them. To realize these necessary for
the living activity and extremely complex processes, metabolism in the capillaries, the
 64
cardio-vascular system has a definite functional structural organization. In the blood
circulation system various physical phenomenon take place.
The hemodynamic indices of the blood flow are determined by the parameters of the
whole cardio-vascular system (for example, the stroke volume of the heart), structural
peculiarities of the vessels (their radius and elasticity) and the properties of the blood itself
(viscosity).
For description of a number of processes occurring in the cardio-vascular system,
methods of physical analogy and mathematical modeling are used.
The cardio-vascular system is a self-consistent complex system with a reciprocally
negative feedback.

Rheological Properties of the Blood

Rheology (from Greek word rheos meaning flow and logos meaning theory) is a
science about deformation and fluidity.
Under blood rheology (hemorheology) the study of biophysical properties of the
blood is understood as a viscous liquid.
Blood as a non-newtonian liquid. Blood flow in large (aorta, arteries), small (arterioles) and
micro (capillaries) vessels
Blood is considered as a non-newtonian liquid, it is greatly related to the fact that it has an
internal structure, it represents a suspension of formed elements in the plasma solution.
Plasma practically is a newtonian liquid. Since 93% of the formed elements are erythrocytes,
in a simplified consideration the blood is an erythrocyte suspension in the physiological
solution. One of the characteristic properties of the blood is its tendency to form aggregates.
If the blood smear is put on the microscope stage, then it can be seen how the erythrocytes
stick together forming aggregates, which are called monetary columns. Conditions for
aggregate formation in large and small vessels are different. First of all it is connected to the
ratio of dimensions of the vessel and erythrocytes. d er ≈ 8 mcm and d agg. ≈ 10d er. 1 mcm=10-
6 m.
Schematic pictures of erythrocyte structure in different parts of vessels
 65

1. Large vessels (aorta, artery). d ves. > d agg. ; d ves >> d er.
dv
In this case velocity gradient (shear) is not great, erythrocytes are collected in
dz
aggregates like monetary columns. Blood viscosity is relatively great and is about η = 0.005
P·s.
2. Small vessels (arterioles) d ves. ≈ d agg. ; d ves. = (5 − 20 )d er .
Here dv/dz is large, and aggregates are broken down to separate erythrocytes, and viscosity
of the system decreases. For this system, the smaller is the diameter of the cross section of the
vessel, the smaller is blood viscosity. In vessels with 5der, blood viscosity makes 2/3 of that in
large vessels.
3. Capillaries d ves. < d er .
In real vessel erythrocytes are easily deformed resembling bells and can pass across capillaries
of diameter 3 mcm without breaking. As a result, the erythrocyte contact surface with the
capillary wall increases as compared to undistorted erythrocyte, improving matter exchange
processes.
If we assume that in cases 1 and 2 erythrocytes do not deform, then for description of
viscosity we can use formula η′ = η(1 + kc ) , where the difference in the geometrical k factor
(shape and sizes) for the system of aggregates ( k agg ) and for a separate erythrocyte ( k er )
k agg ≠ k er must be taken into account, which causes the difference in the blood viscosity in
large and small vessels.
The mentioned formula is not applicable for processes in capillaries because in this
case the admissions about the homogeneity of the medium and hardness of particles are not
observed.
Thus, the internal structure of the blood, and consequently its viscosity too are not the same
along the whole length of the blood vessel due to the differences in the regimes of the flow.
 66
The blood is a non-newtonian liquid: the viscosity force in the blood do not obey to Newton
n
 dV 
formula and is nonlinear. F ∝   .
 dz 
In flowing in large vessels the characteristic viscosity of the blood in norm is about
η blood = (4.2 − 6 )η water , in anemia it is η blood = (2 − 3)η water and in polycythemia it is
η blood = 12 η water .
Water viscosity is 0.01 puas (1 puas=0.1 P·s).
As for any liquid, blood viscosity increases at lowering the temperature. For example, at

lowering temperature from 370C to 170C, the blood viscosity increases by 10%.

Regimes of the blood flow: laminar and turbulent flows

Laminar flow is the regular motion of the liquid when its flow can be represented as a
stationary flow of parallel layers (Fig a)).

For the laminar flow characteristic are smooth (plane) quasiparallel trajectories. In the case
of the laminar flow velocity changes in the cross section of the tube by the parabola law
 x 2 

V = V0 1 − 2
 R 
 
where R is the tube radius and x is the distance from the axis. V0 represents the axial
(maximal) velocity of the flow. When the velocity of the motion is increased, the laminar
flow can transform into turbulent flow. In this case the layers are intensely mixed together,
and numerous vortices of different sizes are created in the flow. Particles begin to make
chaotic motions with complicated trajectories. For the turbulent flow characteristic is the
irregular changing of velocity at all points of the flow. The concept of averaged velocity of
motion can be introduced. The flow properties are essentially changed, in particular, the
structure of the flow, velocity profile, and resistance law. The profile of the averaged velocity
differs from the parabolic profile of the laminar flow. Near the walls it grows more rapidly
and near the center the profile is less curved being described by the logarithmic law. The
regime of liquid flow is characterized by the Reynolds number. In the case of flow in
cylindrical tubes
2RVρ
Re = ,
η
Where v is the flow velocity averaged over the cross section of the tube, R is tube radius, ρ is
liquid density and η is viscosity.
When Re is less than the critical value Recr≈ 2300, the flow is laminar, and if Re> Recr, it
becomes turbulent. As a rule, the blood flow in vessels is taken laminar. However, sometimes
turbulence can emerge. In aorta, turbulent motion of blood can arise first of all due to the
turbulence of the entering blood, vorticity exists from the beginning, when blood is pushed
 67
from the ventricle to aorta, which can be well seen in Doppler cardiography. At the places of
branching of vessels as well as in the case of the increase of the velocity of blood flow (for
example, at muscle functioning), flow can be turbulent in arteries too.
Turbulent flow is connected with the additional waste of energy and in the cardio-vascular
system this can lead to the additional burdening of the heart. The noise arising in case of
turbulent motion can be used in diagnostics. When heart valves are damaged, the so called
heart murmurs arise due to the turbulent blood stream.
Basic Law of Hemodynamics
Hemodynamics is one of sections of biomechanics which studies the laws of the blood flow
through the blood vessels. The main subject of hemodynamics is to establish an
interconnection between basic hemodynamical indices, as well as to their dependence on
blood and vessel parameters. The basic hemodynamical indices include pressure and velocity
F
of the blood flow. Pressure is the force acting on the vessels per unit area P = .
S
Volumetric and linear flow velocities must be distinguished. Volumetric velocity Q is equal
to the liquid volume passing across the cross section of the tube in unit time
V
Q= . Its unit is m3/s.
t
Linear velocity represents the distance covered by the blood particles in unit time
l
V = . Unit of measurement is m/s.
t
Since linear velocity is not the same across the section of the tube, further we will mean the
average velocity.
The linear and volumetric velocities are related by the simple law Q = V ⋅ S , where S is the
area of the cross section of the tube.
Since liquids are incompressible (that is, their density everywhere is the same), the liquid
volumes passing across any cross section of the tube will be the same
Q = VS = const .
This is called the condition of continuity of the stream. It follows from the law of
conservation of mass of mass of incompressible liquid. In description of physical laws of the
blood flow in vessels it is admitted that the amount of the blood mass participating in
circulation remains constant.
From here it follows that the volumetric velocity of the blood flow across any section of the
cardio-vascular system also is constant; Q=const.
In case of real (viscous) liquids flowing uniformly along tubes, their potential energy is spent
on work against internal friction, therefore along the vessel the liquid pressure falls. In
cylindrical vessels with constant cross section for laminar flow of the liquid valid is
Poiseuilles formula

πR 4 ∆P
Q=
8ηl
Where ∆P = P1 − P2 is the drop in pressure, that is, the difference of pressures at the
entrance, P1, and exit, P2, on distance l (see picture)
 68

8ηl
This law has been theoretically given by Gaghen (1839) and Poiseuille (1840). W = is
πR 4
called hydraulic resistance. Therefore we can write
∆P = QW .
From Poiseuille’s law it follows that the drop in the blood pressure depends on the
1
volumetric velocity and also greatly on the vessel radius (since W ~ ). Thus, if the radius
R4
is decreases by 20%, the drop in pressure increases more than 2 times. It is not accidental
that drugs regulating blood pressure act primarily on the lumen of the vessels.

Framework of applicability of Poiseuilles law.

1. laminar flow 2. homogeneous liquid
3. straight hard tubes 4. disturbance spreading far from its source
Kinematics of Blood Flow in Elastic Vessels. Pulse Wave, Velocity of its Propagation
on Vessel Parameters
One of important processes is the propagation of the pulse wave. If we register the
deformation of the of the artery walls at two points at different points apart from the heart,
we will observe that the deformation reaches to the farther point later, that is, there is a
propagation of the wave of oscillations of the vessel volume, blood pressure and velocity of
the blood flow uniquely connected with each other.
The pulse wave is the propagation of the process of the change in the volume along
the elastic vessels due to the simultaneous change in the pressure and liquid mass in it.
In Fig a) the changes in the vessel volume are represented for a few successive moments of
time t 1 < t 2 < t 3 .

Let us consider characteristics of the pulse wave. The wave width P0(x) we will call the
difference between tha maximal and minimal pressures at the given point. At first, in aorta,
 69
the wave width P0,max is equal to the difference of systolic and diastolic pressures P0,max=Ps-Pd
(Fig.b). The shaded area is the range of change in pressure in the large vessels caused by the
propagation of the pulse wave through them.
Damping of the systolic and diastolic pressure difference in the pulse wave during its
propagation along the vessel can be represented by the following dependence
P0 (x ) = P0, max ⋅ e −βx ,
where β is the damping coefficient which increases with the decrease of the vessel radius.
The speed of propagation of the pulse wave depends on the properties of the blood and
vessel:
Eh
Vp = ,
2rρ
Where E is the elasticity modulus of the vessel wall, h is thickness of the wall, r is the inner
radius and ρ is blood density. (This formula was first derived by famous English scientist T.
Young. Then he was an author of classical works on the theory of blood circulation. His
whole life was devoted to two specialities, physician and physicist).
The speed of the pulse wave has been determined experimentally and makes Vp = (6 − 8) m/s ,
which is 20-30 times greater than the speed of motion of the blood particles:
Vbl. = (0,3 − 0,5) m/s . At pushing out of blood from the ventricles (systole), ts =0.3 s, the pulse
wave covers a distance
Lp = Vp ⋅ t s ≈ 2,5 m .
It means it will involve all large vessels, aorta and arteries. The experimental definition of
the speed of the pulse wave lies at the basis of diagnosis of the state of vessels.
With age E increases 2-3 times and consequently the speed of the pulse wave increases too.
Together with the pulse wave, in the blood-vessel system sound waves can propagate too,
whose speed is much greater than that of the blood particles and pulse wave. So, in the
blood-vessel system three basic processes of motion can be distinguished:
1. Displacement of blood particles (Vbl. ≈ 0,5 m/s )
2. Propagation of pulse wave (Vp. ≈ 10 m/s )
3. Propagation of sound wave (Vs. ≈ 1500 m/s ) .
Let us consider hemodynamic indices in different parts of the vessel system.
Hydraulic resistance, W Hydraulic resistance greatly depends on the vessel radius. Ratio of
radii in different parts of the vessel system:
Raorta:Rart:Rcapil =3000:500:1
1
Since hydraulic resistance greatly depends on the vessel radius W∝ , then it follows
4
R
Wcapil>Wart>Waort
Linear velocity of blood flow. Let us consider the law of continuity of the stream
Q=VS=const.
The total net cross section (lumen) of all capillaries 500-600 times exceeds the internal cross
1
section of aorta. It means that Vcap~ ≈ Vaorta.. Consequently in the capillary net, because
500
of slow flow exchange of substances takes place between blood and tissues. In Fig. a the
distribution of the linear velocities is presented along the vessel system.
 70

Distribution of the averaged pressure.

When the hearts contracts, the blood pressure in the aorta makes oscillation.
We will deal with the averaged pressure. The mean pressure can be estimated by formula
P − Pd
Pa=Pd + s
3
The fall of the averaged pressure along the vessel can be described by Poiseuills formula.
Since Q=const., and Wcap>Waort, then for the mean values of pressure fall we will
∆Pcap>∆Part>∆Paort
In the large vessels the mean pressure falls by only 15% and in small vessels by 85%.It
means that the energy of the left ventricle is pushing the blood is mostly spent on the
flow is small vessels.
Distribution of pressure (which exceeds the atmospheric pressure) in different part of the
vessel system will be represented as follows (see. Fig.). The negative values of pressure
correspond to pressures which are less than the atmospheric pressure Ps=16kpa Pd=11kpa.

Frank Model
In 1899, German physiologist Frank developed theoretically an idea that the arteries store
the blood during the systole and push it into small vessels during the diastole.
Let us find the time change in the hemodynamical quantities (e.g., in pressure) at some
point x of a large vessel (aorta).
In the graph, the experimentally obtained variations of pressure P in the cavity of the left
ventricle and aorta are represented as well as that of the volumetric velocity Qs of the
blood pushed from the heart into aorta. It can be seen that P and Qs change over time
nonlinearly.
 71

Curve I corresponds to the first contraction, curve II is its repetition. Dashed line
represents pressure in the aorta and the continuous line that in the left ventricle. Points 1
and 1՛ correspond to the opening of the aortal valve, point 3 to its closure. Point 2 indicates
the moment of time when Qs reaches to its maximal value.
For convenience let us separate two phases of the blood flow in the system of the left
cardiac ventricle: large vessels and small vessels.

In the Frank model the following admissions are made

1. All the large vessels are united in one elastic vessel (reservoir), whose volume is
proportional to pressure. Therefore the reservoir possesses great elasticity. The
hydraulic resistance of the vessel is neglected.
2. The microvesssel system is represented as a hard tube. The hydraulic resistance of a
hard tube is great. The elasticity of small vessels is neglected.
3. For each group of vessels elasticity and resistance are constant in the space and in the
time.
4. The transition processes of establishment of the blood motion is not considered
5. There exists an external mechanism of opening and closing of the aortal valve, which
is determined by the active functioning of the heart.
 72
Let us construct a system of equations for the depicted processes. The change in the volume
dV
of the elastic reservoir, , is equal to the difference of the rate of the inflow into it of
dt
blood Qs and the outflow to the microvessel system Q
dV
= Qs − Q . (1)
dt
Suppose the change in volume of the reservoir is linearly dependent on the change in
pressure in it
dV = CdP , (2)
1
where C is elasticity, the coefficient of proportionality between pressure and volume C ∝ .
E
Using Poiseuilles’s formula for the blood flow of in hard tubes, we will find

P − Pout
Q= (3)
W
where P(t) is the pressure in the large vessels including at the entrance of the hard vessels
and Pout is pressure at the exit of them and W is the hydraulic resistance. In all equations P is
understood to be the surplus pressure (difference between actual and atmospheric pressures).
The system of equations (1,2,3) can be solved for P(t), Q(t) or V(t). By solving for P(t), we
will obtain
dP P Q P
+ = s + out (4)
dt WC C WC
This is an inhomogeneous equation, whose solution is found by the form of Q s (t ) . From the
theory of differential equations, we have
−
t  t 
1  Pout  WC
P(t ) = e   +  ⋅ + ,
C ∫  s
WC Q e dt k
W  
 
where k is found from the initial conditions. Here is the graph of function P(t) obtained from
the above equation when
Q c (t ) = −at 2 + bt ,
Q 2Q max
a = max 2
and b = , (5)
t0 t0
And Qmax is the maximal blood flow pushed from the heart, t0 is the half of the duration of
 t 
the first phase.  t 0 = 1 
 2
 73

Second phase. Since blood is no more pushed from the heart, Q s = 0 , and so the first
equation transforms to
− Qdt = dV , (6)
Where the “-“ sign indicates that the volume of the large vessel is decreasing by time.
Taking into account the third equation, and adopting Pout = 0 (since Pout << P ), we will
obtain the following differential equation
dP P
−C = . (7)
dt W
Solving it we will obtain the law of changing of pressure in the vessels after the aortic valve
has been closed
t
−
P(t ) = Ps e WC (8)
This is the graph of dependence of pressure on time.
 74

Some time t2 later the pressure falls to the diastolic pressure

t
−2
Pd = Ps ⋅ e WC ’
After which the second phase ends and the first begins.
From equation (4) if we neglect Pout, we obtain
dP P Q
+ = s.
dt WC C
Multiplying it by dr and integrating we obtain
Ts Pd T
1 s
∫ Q s dt = CP ∫ dP + ∫ Pdt .
W 0
0 Pd
Pd Ts Ts T
s
1
Integral ∫ dP =0, and so ∫ Q s dt = ∫ Pdt . This integral ∫ Q s dt represents the stroke volume
P 0 W 0 0
d
of the blood representing the volume of blood pushed by heart into the aorta during one
systole. The stroke volume of the blood can be found as the square area under the graph of
1 Ts
blood pressure dependence on time devided by hydraulic resistance ∫ Pdt .
W 0

kP
This is the electric model of the heart
 75
§1P. SURFACE TENSION OF LIQUIDS, COEFFICIENT OF TENSION

The area of the liquid surface, contacting with another medium, for example with its
own vapors or another liquid or solid (in particular, with the walls of the vessel in which it is
contained) finds itself in peculiar conditions compared with the rest of the liquid mass.
These peculiar conditions arise because the molecules near the liquid boundary (Fig.1,
molecule A) in contrast to molecules in the bulk of the liquid (Fig.1, molecule B) are
surrounded by the molecules of the same liquid not from the all sides. Therefore, the
molecules near the surface layer of the liquid having different “neighbors” interact
differently with these molecules. Thus, the forces acting on each molecule of this layer are
unbalanced, a resulting force arises, which is directed either into the same liquid or to the
neighboring medium (Fig.1).

In Fig.1 the resulting force acting on the molecule A near the surface is directed to
inside the liquid, and doing a positive work tries to lessen the surface area of the liquid. The
resulting force acting on the molecule B in the bulk of the liquid equals zero. So, moving
from the surface to the depth of the liquid the molecule does a positive work. And vice versa,
the transition of molecules from the bulk of the liquid to the surface area is accompanied by
a negative work, that is, the external forces do the work.
If the liquid surface area at constant temperature has changed by amount dS, then the
necessary work dA will be given by formula
dA=-σdS, (5.1)
where constant factor σ is called coefficient of the surface tension and characterizes the
given liquid. The negative sign in (5.1) shows that the increase in the surface area dS>0 is
accompanied by a negative work. From this definition it follows that σ is measured in
J N
= .
m2 m
Every system tends to a state with minimal free energy. Therefore, along the liquid
surface forces are acting, which tend to decrease its surface area. These are forces of surface
tension.
Some liquids, for example lather, can create thin layers. If we dip a wire frame with
one mobile side (AB) into suds, it will fill the frame (Fig.2)
 76
Forces of surface tension make the layer shorten moving the mobile wire stick AB move
upward. Therefore, the forces operating in the layer are perpendicular to the stick AB, which
represents a border of separation. It is clear that forces act also on the other sides of the
rectangle.
Suppose, under the action of the force of surface tension the stick AB has traveled
distance dh. Thaw work done by it will be
dA=fdh. (5.2)
According to definition (5.1), dA=-σdS, where dS=-ldh, hence dA is given by
dA=σldh (5.3)
Equating expressions (5.2) and (5.3), we obtain
f
σ= . (5.4)
l
The coefficient of surface tension is determined by the forces of intermolecular
interaction and characterizes the liquid itself. With increasing temperature (if far from the
critical temperature) σ decreases almost linearly.
Wetting (wettable) and non wetting liquids. The interaction between the liquid particles
filled in a vessel and the solid body affects also the shape of the liquid surface. If a large
amount of liquid is filled in a broad vessel, then the shape of the liquid surface is dictated by
the gravity force, which naturally provides a smooth and horizontal surface.
But in areas very close to the walls the liquid surface is curved and a meniscus is
formed, which is concave for wetting liquids (Fig.3a) and convex for nonwetting liquids
(Fig.3b).

Fig.3
Because of the phenomenon of wetting and nonwetting, at the border of separation
of liquid and solid body the liquid forms either a droplet on the solid surface (hydrophobe
surface), or spreads as a monomolecular layer over it (hydrophilous surface).
Capillary phenomena. Laplace formula. The curving of the liquid surface leads to a
creation of an additional pressure on the deep layers. Beneath the spherical surface the liquid
volume finds itself always compressed under the action of forces of the surface tension, in
other words, it undergoes an additional pressure. Because of that pressure the radius of the
liquid sphere has decreased by dr and the volume by dV. The work of compression is given
by
dA=-pdV (5.5)
At the same time, according to definition (5.1)
dA=-σdS (4.6)
The surface area of a sphere and its volume are given by formulas
 77
4 3
S=4πr2 and V = πr respectively.
3
From these formulas we get
dS=8πrdr and dV=4πr2dr. (Note, that dr<0)
Putting these values in expressions (5.5) and (5.6) we get
2σ
p= , (5.7)
r
Which is called Laplace formula.
Capillary phenomena. Because of interaction of the liquid with the vessel walls, the forces
of surface tension tend to raise or lower the surface level in the tube. If the walls of the tube
are wetting for the given liquid, the liquid is raised, in the opposite case it is lowered.
Suppose the liquid has been raised by some amount h, and at equilibrium the hydrostatic
pressure is balanced by the pressure created by the curvature of the surface (Fig.4)
2σ 2σ cos θ
ρgh = = , (5.8)
R r
where R is the radius of curvature of the liquid surface and R is the tube radius. Height h can
be determined from (5.8)
2σ cos θ
h= . (5.9)
ρgr

Fig. 4

If the radius of curvature of the liquid surface and the tube radius are of the same order of
magnitude, then the tube is called capillary and the phenomena taking place in it capillary
phenomena.
Capillary phenomena play a great role in the animal and plant life. It is thanks to
this phenomenon that water reaches trough the tree shoots /scions/ to heights of several tens
of meters, etc.
Embolism
Consider the behavior of the air bags in a liquid in the capillary. If the liquid pressure
on the bag is the same from all sides, both bag meniscuses will have the same radii, and the
 
forces of additional pressure will be balanced F1 = −F2 . At surplus pressure on one side, for
example, at movement of the liquid, the meniscuses deform, their curvature radii change and
the surplus pressures ∆p on different sides become unequal (Fig. 5). This leads to such an
action of the air (gas) bag on the liquid which hampers the movement of the liquid or even
can stop it.
 78

Fig. 5
This type of phenomena can take place in the vascular system of men. The air bubbles
penetrated into the blood can block a small vessel and stop blood supply of an organ. This
phenomenon called embolism can lead to a serious a functional disruption or even to death.
For example, air embolism can follow the injuries of large vessels; the air penetrating into the
blood stream produces an air bag hampering the blood flow. Air bags should not get into
veins at intravenous infusions.
Gas bubbles can emerge in divers at rapid lifting from deep depths to the surface, in
pilots and astronauts at depressurization of cockpits or space-suit on big altitudes (gas
embolism). This is caused by the transition of gases in the blood as a result of fall of the
surrounding atmospheric pressure from the dissolved state to a free state. The leading role in
the formation of gas bubbles at pressure decreases belongs to nitrogen since it constitutes the
main part of the total gas pressure in the blood and does not take part in the gas exchange
between the organism and the ambient air.
Confer Alveolar Stability
On the basis of Laplace law, air would be displaced from the smaller alveolus into the
larger one and the smaller alveolus would thus become still smaller. This process would
continue until the smaller alveolus would collapse entirely while displacing all of its air into
the larger one. This process would lead to instability of alveoli (Fig. 6). But this instability is
prevented by surfactant. Surfactant is a lipoprotein mixture secreted by special surfactant-
secreting cells, i.e. type II granular pneumocytes present in alveolar epithelium. It is a surface
tension lowering agent. As an alveolus becomes smaller the surfactant becomes more
concentrated at the surface of alveolar lining fluid. Hence, surface tension becomes
progressively more less. On the other hand as an alveolus becomes bigger, the surfactant is
spread more thinly on the fluid surface. This

Fig. 6
increases the surface tension. This property of surfactant stabilizes the sizes of the alveoli,
causing the large alveoli to contract more and the smaller ones to contract less. The absence
of surfactant in the alveolar membrane of of some premature infants causes the respiratory
stress syndrome in them.
79
 A B
1) Find the formula of equilibrium intermolecular distance if F r    
r 7 r13

B 2A 13B A
1) 6 2) 6 3) 6 4) 6
A B 7A B

2) It is not a unit of measurement of polarizability (  )

C2  V C2  m C  m2 C2  s2
1) 2) 3) 4)
N N V kg

3) Trajectory of particles of ideal gas making irregular thermal movement in the general case …

1. is a scalene (inequilateral) broken line 2. is an equilateral polygon

3. is continuous 4. is open

4) In plasma state matter can be ...

1) at any temperature 2) only at very high temperatures

3) only at very high pressures 4) only in stars

5) Which of the following graphs might describe the melting process of a amorphous solid body?

1) 4 2) 2 3) 3 4) 1

1
6) Which of the following diagrams might describe the melting process of a crystalline solid body?

1) 1 2) 2 3) 3 4) all are possible

7) Dynamic viscosity coefficient   is numerically equal to

2
1) friction force acting on 1 m in case of unit velocity gradient

2
2) friction force acting on 1 m

3) friction force acting on surface S in case of unit velocity gradient

4) friction force acting on surface S

8) Which of the following statements is wrong? Transport phenomena …

1) can occur only in case of density or non-homogeneity of particles concentration

2) can occur only in case of non-homogeneity of certain magnitude

3) occur in gases and liquids

4) can be conditioned by non-homogeneity of directional movement velocity of the particles

9) Which of the following formulas are right?

2  1
1. For uniformly changing quantity  , gradient on x axes equals:
x
2. In transport phenomena, flux of quantity  occurs in direction of the increase of that quantity

3. I       x 
2
4. Gradient of quantity  is called change of  on unit length

10) Diffusion coefficient for gases is determined by ...

12 1 2 2
1. D 2. D  v 3. D  n v 4. D
3  3 3 32

11) What is the cause of thermal conductivity?

1) non-homogeneity of temperature

2) non-homogeneity of concentration

3) non-homogeneity of velocity of particles’ directed movement

4) flow of heat quantity

12) During thermal conductivity phenomenon, the direction of heat flow does not coincide with …

1) direction of temperature increase

2) direction of temperature decrease

3) opposite direction of temperature gradient

4) direction of decrease of T ( x) function

13) What is wrong for viscosity?

1) Viscosity is caused by the heat transfer between gas layers moving at different velocities

2) Viscosity is caused by the particle momentum transport between gas layers moving at different velocities


3)   4) Momentum flux is perpendicular to the velocity of moving layers

14) What is wrong for viscosity?

1) Momentum flux from one layer to the other is directed opposite to the velocity of moving layers

3
 
2)   3) Momentum flux is perpendicular to the velocity of moving layers

4) Viscosity is caused by the particle momentum transport between gas layers moving at different velocities

15) Those liquids are called Newtonian whose viscosity coefficient depends on ...

dv
1. only velocity gradient ( ) 2. only friction layers surface (S)
dr
dv
3. only friction layers thickness 4. both , and S
dr

16) Viscosity of Newtonian liquids …

 B
1. depends on temperature 2. is determined by   A exp    formula
 T
dV
3. does not depend on liquid flow characteristics 4. depends on velocity gradient of liquid flow
dx

17) Which statement is wrong for suspension viscosity formula   0 1  kc  ?

1)  0 is viscosity of the solution at t 0 2)  0 is viscosity of the solvent

3) k depends on geometric structure of particles 4) C is concentration of dissolved particles

18) Liquid flow is turbulent, when…

1) starting from the certain value of flow velocity, which depends on liquid’s properties and pipe’s diameter, the storms
begin to appear

2) layers velocity magnitudes are different

3) starting from the certain value of flow velocity, which doesn’t depend on liquid’s properties and pipe’s diameter, the
storms begin to appear

4
 2 RV 
19) Which statement relative formula of Reynolds number: Re  , is wrong?

2 Rm
1) Re  , where m  V , is liquid mass 2) Reynolds number depends on liquid temperature

2 RV 
3) Reynolds number is dimensionless 4) Re  , where   , is kinematical viscosity
 
20) In case of liquid laminar flow, the velocity along pipe’s axis is changed by … law

1) is not changed 2) linear 3) logarithmic 4) cubic

21) In case of liquid laminar flow through cylindrical pipe, the liquid velocity at the pipe’s walls …

1) is equal to 0

2) accept a maximum value

3) can be modified randomly

4) is equal to liquid velocity on pipe’s axis

 x2 
22) In case of laminar flow through cylindrical pipe, which of the statements regarding V  x   V0  1  2  formula
 R 
is wrong?

1) Liquid layer velocity is depending on the pipe’s radius according to the quadratic law.

2) V0 - is central payer velocity in the pipe

R
3) V  0  V0 4) V    V0
2
23) How many times is the velocity V0 of the liqud layer flowing along the axis of the cylindrical tube greater than that of

R
the layer at distance x from the axis at laminar regime of flowing.
2

1) 2 2) 2 3) 1 4) 0.5

5
24) How many times the vessel’s hydraulic resistance will be changed, if in consequence of the taken drug the blood
viscosity was decreased by 25% and the vein radius was increased by 25%.

1) 0.3072 2) 2.7648 3) 0.1062 4) 4.1278

25) The coefficient of surface tension is numerically equal to ... and is measured in unit ...

1) the work done by external forces at increasing the liquid surface area by a unit:   dA / dS ; J / m2
2) the ratio of the work to increase the liquid surface area to the length of the surface contour:   A / l ; J / m2

3) the ratio of the force of surface tension to the surface area:   F / S ; N / m2

4) the ratio of the force of surface tension to the Laplacian pressure   F / P ; N / Pa

26) Due to phenomena of surface tension ...

1) more water can be filled in glass than its capacity is 2) nutrition of animals takes place

3) sea billows 4) rubber baloon tends to be coռtracting its surface

27) Forces acting on a molecule in the surface layer of the liquid from other molecules …p

1. are balanced 2. are unbalanced

3. have a gravitation nature 4. tend to increase the surface area of the liquid

28) Surface tension forces …

1. have gravitational nature 2. have electromagnetic nature

3. are determined by formula dA   dS 4. tend to decrease the free surface area of the liquid

2 cos
29) Wich statement about the the hight of the liquid column: h in a capillary caused by surface tension
 gr
forces is incorrect?

1)  is the vessel inclination towards horizon 2) r is vessel radius

6
3)  is liquid density 4) g acceleration of the free fall
2 cos
30) Wich statement about the the hight of the liquid column: h in a capillary caused by surface tension
 gr
forces are correct?

1.  is the coefficient of surface tension of the liquid 2. r is vessel radius

3. g acceleration of the free fall 4.  is the density of vessel material

31) The force of surface tension ....

1) does a positive work when the free surface area of the liquid is decreased

2) F S 3) does work: dA   dS 4) does work: dA   dl

32) The external force ....

1) does a negative work when the free surface area of the liquid is increased

2) F S 3) does work: dA   dS 4) does work: dA   dl

7
1) Which of the following statements is wrong for an isobaric process?

1) VT  const 2) V is directly proportional to T

T V
3)  const 4)  const
V T
2) Նկարում պատկերված է հաստատուն զանգվածով իդեալական գազի հետ տեղի ունեցող պրոցեսների
գրաֆիկներ։ Ո՞ր պնդումներն են ճիշտ։
1. Tb  Ta ; c -is isochoric process
2. Tb  Ta ; d - is isochoric process
3. a and b are isothermal processes, e and f - are not isoprocesses
4. e and f - are isothermal processes, c - is isobaric process

3)Նկարում պատկերված է հաստատուն զանգվածով իդեալական գազի հետ կատարված շրջանային

պրոցես: Պատկերի առանձին տեղամասերի համար որ պնդումներն են ճիշտ: P
1. 1  2 isochoric, 4  5 isothermal, 5  6 isochoric
2. 1  2 isochoric, 2  3 isobaric, 3  4 is not isoprocess
3
3. 2  3 isothermal, 4  5 isobaric, 5  6 isochoric 2 4
4. 6  1 is not isoprocess, 4  5 isothermal, V1  V6 1 5
6
0 T
4) Which statement about the the real gas model described by Van-der-Waals equation is wrong (under other similar
conditions)?

1
1) In this model, the pressure caused by the molecular attraction is directly proportional to
V
2) In this model, under similar conditions pressure as compared to the ideal gas due to attraction of molecules, decreases

3) In this model, repulsion between molecules is taken into account through the molecules own volume

4) In this model, internal energy depends both on temperature and volume

5) System consists of two bodies. In thermodynamic equilibrium, which of the following inequalities cannot take place?

1) T1  T2 2) U1  U2 3) S1  S2 4) V1  V2
6) Thermodynamics is the part of physics which investigates matter …

1.without considering interactions of the particle making up the system

2.considering it as a single entity 3.without considering its molecular structure

1
4.taking into account its atomic and molecular structure

7) Which of the following statements is wrong? First principle of thermodynamics …:

1) is valid only in isolated systems

2) represents the law of conservation of energy in heat processes

3) is one of basic laws of nature 4) has been confirmed by many experiments

8) Which of the following statements is wrong? First principle of thermodynamics …:

1) is valid only in isolated systems

2) represents the law of conservation of energy in heat processes

3) is one of basic laws of nature 4) has been confirmed by many experiments

9) Which of the following statements is correct for an isothermic process in an ideal gas:

1. U  Q 2. dU  0 3. A   RT ln V2  V1  4. T  Const

10) According to the First Law of Thermodynamics, if 270 Joule of heat quantity has been transmitted to the system in an
isobaric process, then its internal energy has been changed by…

1) all possible 2) -90 Joule 3) 0 4) 270 Joule

11) Which of the following statements is compatible with the Second principle of thermodynamics?

1. It is possible to implement a process, in the result of which the entropy will reduce

2. The heat can switch from cold body to hot body

3. The Second principle of thermodynamics determines the magnitude and direction of thermodynamic process

4. It is impossible to implement a periodic process, the only result of which will be conversion of heat into work due to
body cooling

12) Which of the following statements are correct:

dQ
1. The function having a complete differential is called entropy
T

2
 2
dQ dQ
2. dQ  TdS 3. S 4. is always a complete differential
1
T T

13) For Boltzmann formula S  k ln W , which statement is incorrect?

1) W is mechanical probability 2) S 0
3) W 1 4) ln W  0
14) Which of the following statements is wrong?

S
1) is inversely proportional to k and grows linearly with decreasing k
I
S
2) W  2I 3) I  log 2 W 4) I log 2 e
k
15) Which statement is wrong for S  Si  Se equation?

1) Si - is entropy change, which is conditioned by the balance processes taking place in the system

2) Se - is entropy change, which is conditioned by interaction of the system with external bodies

3) for unbalance processes Si  0 4

) for stationary processes S  0

16) In stationary state of the system

1. S  const 2. S 0 3. dS  0 4. dS  const

17) Which of the following statements is correct?

Q
1. Unit of can be g 2. Unit of kt can be g/s
k
mk
3. is dimensionless 4. Unit of km –ի can be kg  s
Q

3
18) How long after one-time injection, 10% of the initial quantity of drug in the blood will remain, if drug removal ratio
is K = 0.3 time-1  ln10  2.3 . Express in round numbers.

1)  7.7 2)  6.7 3)  3.4 4)  10.8

19) Picture presents diagrams on drug quantities in organism in case of continuous injection. Which statements are right
for unknown prescriptions available in diagrams and picture?
1. ?3  C0 a , ?4  C0b
2. C0 a  C0b
3. ?1  t , ?2  C
4. ka  kb

20) By which of the following formulas is impossible to calculate optical density of the solution?

ln I 0 I0
1) A 2) A  ln 3) A  ln I 0  ln I 4
) A   cd
ln I I
21) DNA molecule contains N number of paired nucleotides of which N1 number of paired nucleotides are in helical
state and N 2 are in non-helical state. Which formulas for the helicity of the DNA molecule are valid?

N  N2 N1 N1 N 2 N1
1. 2. 3. 4.
N N1  N 2 N1  N 2 N

22) Facilitated diffusion of ions and molecules

1. is a mechanism of passive transport of the substances 2. is done with the help of ion pumps

3. is a mechanism of active transport of the substances 4. is possible to inhibit

23) Which of the following statements is correct?

6 V
1. Near the cell membrane the strength of electric field is about 10
m

2. Electric capacity of unit area of the cell membrane is 0.5 102 F

4
 C J
3. Faradays constant is F  96500 4. Boltzmann constant is k  8.31
mol mol  C

24) Which statements are correct about the action potential?

1. In related experiments squid axon was used 2. In related experiments frog skin was used

3. For cel membrane refractory period exists


4. At cell membrane stimaulation, the membrane permeability towarda K ions increases sharply

25) Which of the following statements is wrong?

1) Ca 2 pump is electrogenic 2) Na   K  pump is electrogenic

3) proton pumps contributes to the formation of hydrochloric acid

4) if Na   K  pump stops working, then membrane potential will decrease

26) Calcium pump ...

1. is an electrogenic pump 2. plays an important role in muscular contraction processes

3. At the expense of the hydrolysis energy of one ATP molecule, one Ca++ ion is transported

4. At the expense of the hydrolysis energy of one ATP molecule, two Ca++ ions are transported

27) Determine  electrochemical potential, if Gibbs energy is G  3C 2   p 2C   T , where  ,  are constant

1) 6C   p 2 2) 6C   p 2C 3) 3C 2   p 2C 4) 6C   T
5
28) Membrane thickness is 3  10 m . Potassium ion concentration inside the cell is 500 mol / m է : At which
3

concentrations of that ion outside the cell, the absolute value of their gradient across the cell would be greater than

9  106 mol / m4 .
1. 350 mol / m3 2. 320 mol / m3 3. 150 mol / m
3
4. 200 mol / m3

5
 For teachers 3
1) Potential differences being investigated in electrocardiography are only in the interval:

1. 0.1  5 mV 2. 104  5 103 V 3. 0,001  0,05 V 4. 0,5  1 mV

2) What is the potential of electric field of current dipole at a point equally distant from the poles?

1) 0 2)    d 3) does not exist 4)    d

4 r
2
4 r

 
3) Potential difference of the electric field of the current dipole D between two equidistant points A and B at

distance r from it if the line AB is parallel to the dipole moment direction, is not found from formula:

1)   0 2) D 3)   KD 4)   (2 r 2 )1  D sin 

  sin 
2 r 2

4) Potential difference between two equidistant points from the dipole …

1. is calculated by formula    D sin  cos

2 r 2

2. is directly proportioanal to the projection of the dipole moment on the line connecting the points

3. is calculated by formula    D cos

2
4 r

4. is directly proportional to the projection of its dipole moment on the chosen x axis
5) What is the potential of electric of current dipole at a point that is at distance 2r from the positive pole and at
distance r from the negative one?

1) 
I 2)
I 3)
I 4)   I
8 r 8 r 4 r 4 r

6) What is the potential of electric of current dipole at point A in the direction of the dipole moment at distance l
from the positive pole?

1) I 2) 
I 3) d 4) 
d
8 l 8 l 8 l 8 l
7) Which of the statements about the first phase of Frank model is correct?

1) The greater part of the blood pushed by heart into aorta is stored in large vessels and the rest goes to small vessels

2) The total amount of blood pushed by heart into aorta is stored in aorta

3) Blood pushed by heart into aorta momentarily goes to peripheral vessels

4) all of the mentioned cases are possible

8) Which of the statements about the first phase of Frank model is incorrect ?

1
1) The volumetric velocity of blood thrust from heart to aorta equals zero

2) Aortal valve is open 3) Q  dV  Q

s
dt

4) In large vessels hydraulic resistance is neglected

9) According to Frank model, after closure of the aortal valve how much time later pressure in aorta will become half
of the sistolic pressure

1) WC ln 2 2) 2WC 3) WC 2 4) WC
2

10) Which statement is wrong about the second phase of Frank model?

1) pressure grows with time by the exponential law

2) pressure decreases with time by the exponential law

t
3) Qs  0 4) Ps  PeWC

11) How would change the speed of the pulse wave if because of organism aging the Young modulus of the vessel
walls increased 3 times, the inner radius of the vessel cross section decreased by 20% and blood density increased by
20%?

1) Would increase 3.125 times 2) Would increase 3 times

3) Would decrease 3 times 4) Would increase 3.875 times

12) With age, …

1. elasticity of the human blood vessel walls decreases

2. Young’s modulus of the human blood vessel walls decreases 2-3 times

3. speed of pulse wave in human blood vessels increases

4. viscosity coefficient of the lipid phase of the human biomembrane increases

13) Which of the following statements is wrong?

1) Quantity  is measured in units: s-1 2) In an elastic medium stress is determined by formula:  el  E

E

3) Relative deformation:    is dimensionless 4) Stress in a viscous medium is directly proportional to d 

dt

14) What is the unit of measurement of quantity E ( E is Young modulus,  is viscosity)?



1) s -1 2) s 3) kg / poise 4) N / poise

2
15) What is the unit of measurement of quantity  (  is stress,  is viscosity)


1) s-1 2) it is dimensionless 3) kg / poise 4) N / poise

16) What is the unit of measurement of quantity E (  is stress, E is Young modulus)?


1) it is dimensionless 2) Pa 3) N 4) s
17) It is not a unit of measurement of mechanical stress   :

1) N  m2 2) poise  s-1 3) Pa 4) N  m- 2

18) Young modulus E numerically equals the stress at which …

1.  1 2. the length of the deforming body triples

3. extension of the deformed body equals its initial length: l0 4. absolute deformation: x  l0

19) In Kelvin-Voigt model, how much time later deformation would become equal to 3 of the stationary value of
4
deformation?

1) t   ln 4 2) t   ln 3 3) t   ln 3 / 4 4) t  E ln 4
E E E 