Faculty of General Medicine

Department of Biophysics and Radiation Biology

Medical Biophysics
Medical Biophysics
Introduction
Prof. Judit Fidy
?

Medical biophysics --- ? Medical biophysics --- ?

‡ Biophysics ± scientific field ‡ Biophysics ± scientific field
- physical methods (experimental
and theoretical) applied to
biological objects
Examples:
Light microscopy + fluorescent dyes Present day resolving power of determining
X-ray diffraction on crytals of biological macromolecules structural data
Æ Structural information about cells, molecules in atomic details
X-ray scattering data are collected, direct measurement
evaluation is by fitting a structural by sophisticated
X-ray diffraction: model by computer microscopy techniques
Structural model of globular actin
gray - C; red - O; blue - N; yellow - S

G-actin
(d=5 nm)

1 nm

Fluorescence microscopy on cells labelled by Oxygen atoms on the surface of a

dyes binding to actin filaments Structural model of globular actin rhodium single crystal
gray - C; red - O; blue - N; yellow - S (scanning probe microscopic image)

Actin filament (d=7 nm)

Example : Drag coefficient of a sperm cell

Medical biophysics --- ?
How much force (F) is necessary for a sperm cell to be transported in a medium?

Simplified sperm cell model:

‡ Biophysics ± scientific field
object with circular cross-section Stokes䇻 Law:
- physical methods applied to
biological objects
- observing biological phenomena Æ
F = v = 6r v
(new physical descriptions) Æ
= 6r = 6 ×1.6 10 6(m)× ×10 3(Pas) = 3 10 8 Ns/m understanding biology Æ learning
8 5 12
F = v = 3 10 Ns/ m×5 10 m /s = 1.5 10 N = 1.5 pN
Æ influencing
 Mechanisms behind cell motility? ‡ Medical biophysics
How does it happen (what is the exact mechanism)? Building a predictive model.
- physical methods applied to biological objects Æ
Structure Functional test:
䇾In vitro motility assay䇿
Dynein
Æ diagnostics, therapy
MT

- observing biological phenomena Æ new physical

descriptions Æ understanding biology Æ learning,
Cover glass
Fluorescence microscopy
Step size: 8 nm
(distance between
Æ targeting of medications, nanotechnology
every other
tubulin subunit)
*Note: Figure shows
kinesin, and not dynein!
for internal monitoring and substitution of
impaired physiological functions

*Note: Figure shows kinesin-dependent motility!

The course The course

Lectures: topics needed as foundation for

Lectures: topics needed as foundation for medical practice
medical practice - not malpractice!
Laboratory practices:
Laboratory practices: goal: learn how to design and peform
goal: learn how to design and peform
experiments
experiments
how to evaluate the data and how to evaluate the data and
to draw conclusions to draw conclusions

Preparation for medical practice

 Lecture topics
Semester I.
1. Length scale of biology. Atomic physics
2. Electromagnetic radiation. Dual nature of
light. Matter waves
3. The atomic nucleus. Radioactivity. Nuclear
radiation
4. Interaction of electromagnetic radiation with
matter
5. Radioactivity in the medical practice.
Dosimetry, nuclear medicine
6. Luminescence
7. Laser and its medical applications
8. X-ray
9. Multi-atom systems. The Boltzmann
distribution
10. Molecular biophysics. Water,
macromolecules, biopolymers
11. Nucleic acids and proteins. Folding of RNA
and proteins
12. Atomic and molecular interactions. Scanning
probe microscopies
13. Biomolecular structure. Diffraction, X-ray
crystallography, light- and electron
microscopy. Mass spectrometry, CD
14. Biomolecular structural dynamics.
Fluorescence, ESR, NMR. Basics of MRI
$WRPLFÄERXQG´HOHFWURQV± quantum numbers
The energy and the momenta of the electron in the atom can have only well defined, discrete
values
Angular momentum and spin momentum
absolute value direction
L m
v
r
Towards complexity ?
Semester II.
6WDUWLQJIURPÄVLPSOH´the atom ( simplification: composed of elementary particles)
1. Gas laws. Pulmonary biophysics
2. Thermodynamics. Thermodynamic system, laws ÄRUELWV´RIHOHFWURQVERXQGWRWKHQXFOHXV
3. Equilibrium and change. Kinetics. Entropy an its schematics
microscopic interpretation - probability distribution functions
M
4. Irreversible thermodynamics. Transport processes. L - each orbit means a discreat energy status of e-
Diffusion, Brownian motion
- ./0«ODEHOVPHDQLQJQ 
Complexity
5. Cytoskeletal system. Motor proteins. Mechanisms of
biological motion
6. Biomechanics. Biomolecular and tissue elasticity
d~10-10 m Free
7. Fluid dynamics. Circulatory biophysics
electron
8. Muscle biophysics. Striated muscle, smooth muscle (QHUJ\PHDVXUHGLQÄH9´XQLWV
9. Cardiac biophysics. Work of the heart. The cardiac
Energy states of bound electrons
cycle H-atom
10. Bioelectric phenomena. Resting potential
11. Action potential. Biophysics of electrically active
tissues. EKG, EMG, EEG. Principles of sensory
function
12. Sound, ultrasound. Auditory biophysics
13. Optics of the eye, biophysics of vision Orbital electrons (-) Atomic nucleus
14. Collective processes in ensembles. Complex systems,
d<10-18 m Proton (+)
networks Neutron
Free electron
d~10-15 m
d~10-14 m
Quantum numbers and the periodic table
Characterization of bound atomic electronic states: with n, l, ml, ms quantum numbers
n ĺHOHFWURQVKHOO
n, l ĺHOHFWURQVXEVKHOO
n, l, ml ĺHOHFWURQRUELWDO
s ±spin state
both magnitude and direction are discrete
Friedrich Hermann Hund
Wolfgang Pauli (1900- (1896-1997)
1958)
Hund principle:
Pauli䇻s exclusion principle:
‡Order of filling up the quantum states.
‡Each quantum state can be ‡For a given electron configuration, the state with
maximum total spin has the lowest energy.
occupied by a single electron.
‡Within an atom there cannot be two Electron configuration of the C
electrons for which all four quantum atom
s: 䇾sharp䇿, p: 䇾principal䇿, d:
numbers are identical. 䇾deformed䇿 (spectroscopic
nomenclature)
fully occupied partially unoccupied
subshell occupied subshell
 Complexity - shown in dimensions
$WRPLFÄERXQG´HOHFWURQV± interact with photons of Stages of complexity require distinct physical models of
electromagnetic radiation understanding
PHOTONS Thermodynamics 1023 Atoms
The photoelectric effect Observation by F.Lenard: Albert Einstein
1879-1955
light Ejected electrons Kinetic energy of ejected electrons does
not depend on the intensity of light. It
depend solely on the frequency of light Photon:
energy quantum of electromegnetic
Explanation by A.Einstein radiation in interaction with matter
1905
E photon hf c Of
Metal foil
E photon hf Wionization  Ekinetic
1010 Atoms

Way of interaction: An orbital electron is able to change its energy

one photon one electron status to another orbit by consuming/absorbing Mesoscale
or releasing/emitting the energy difference
between the two orbits in the form of
E2 a photon of electromagnetic radiation
103 Atoms
E1 of proper frequency

hf E2  E1 Quantum chemistry 101 Atoms

Quantum physics
100 Atom
Nuclear physics

Paying tribute to the discoverers Paying tribute to the discoverers

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Gold foil
Ernest Rutherford
(1871-1937)
Microscope
Joseph John Thomson
(1856-1940)
ZnS screen
John Dalton (1766-1844). Discovery of the 1909: discovery of the atomic nucleus
Democritus (460-370 BC) Lead
Matter composed undivisible
electron 1897. The positive charge in the atoms is not distributed like
particles (atomos). a jelly, but concentrated within a tiny volume

Dalton䇻s atom of a given element

5QĮ-ray source) Gold foil

D ± particle : heavy atomic nucleus 2p and 2n (2+)

Elements are made of extremely small particles called atoms. Cathode ray (electron beam) in
Atoms of a given element are identical in size, mass, and other properties; atoms of different elements differ in size, vacuum tube.
mass, and other properties.
Atoms cannot be subdivided, created, or destroyed.
Observation: most of the a particles crossed
Atoms of different elements combine in simple whole-number ratios to form chemical compounds the foil undeviated from their path
In chemical reactions, atoms are combined, separated, or rearranged. Rutherford䇻s atomic model:
miniature planetary system
Gravitational force replaced by interaction with positive nuclei was rare
electric attraction
䇾Plum pudding䇿 atomic model:
Electrons revolve in orbits within a
positively charged jelly-like substance
 Paying tribute to the discoverers Paying tribute to the discoverers
Rutherford ± Bohr model 1911-13 Experimental verification of the quantized energy states of bound electrons
1. Quantum conditions for the electron-state:
‡The electrons move around on orbits of quantized angular momentum
Franck-Hertz experiment (1914)
‡On the given orbit the electron does not loose energy ± it is constant and of discrete value
Cathode Lattice Anode
‡.
Niels Bohr (1885-1962)
assistant of Rutherford Hg vapor
n= principal quantum number. The radii of the orbits can be calculated.. The radius of the first orbit is r1 = 5,3 10-11 m (䇾Bohr-
radius䇿 The electrons accelerated by
2. Combines e--energies and the photon concept the lattice voltage (Ulattice),
‡The atom HPLWVUDGLDWLRQRIÄI´IUHTXHQF\only if the elctron 䇾jumps䇿 from one orbit to the other. upon inelastic collision with
‡Energy of the radiation is the difference between the orbit energies:
E photon hf E2  E1 c Of James Franck (1882- the Hg atoms, loose their
The orbit energies can be calculated. Energy of the first orbit is E1=-13.6 eV. Further orbit energies are:
1964) energy in discrete packages
Ulattice -Uanode
(䇾quantum䇿 - sing., 䇾quanta䇿
Energy levels in the hydrogen atom. - pl.).
Bohr model of the hydrogen atom

Achievements
The model explained the spectra of the hydrogen atom.
Quantum-concept included for electron and for radiation

Problems:
Gustav Ludwig Hertz (1887-
Orbiting electrons should radiate according to classical 1975)
mechanics ± orbital energy should not be constant
The orbiting electrons should have measurable magnetic Ulattice
moments
*N.B.: postulate: fundamental requirement,
. condition

Paying tribute to the discoverers Paying tribute to the discoverers

(UZLQ6FKU|GLQJHU
Louis V. de Broglie (1892-1978) (1887-1961)
Imagine a photon or an electron as a wave
1923: wave ± particle duality concept Ä6FKU|GLQJHUHTXDWLRQ´a

The electron as a wave electron wave functions to Werner Heisenberg (1901-1976)

describe the state of the electron
in the atom
Clinton Joseph Davisson (1881-1958)
Lester Herbert Germer (1892-1968) Discrete energies of orbitals
Atomic electrons are considered as standing waves instead of orbiting particles corresponding to wave functions
Uncertainty principle
1927: diffraction pattern with
Quantized behavior in the stationary
waves of a stretched string electrons: wave behavior verified
Ȍ(x,t) wavefunction:
‡ >Ȍx,t)]: gives the amplitude of the electron wave Wave packet view
as a function of position (x) and time (t).
screen
‡ Ȍ2: gives the probability of finding the electron
or electron charge density. functions
Electron beam ‡ Ȍ2: integrated across the entire space = 1 (i.e.,
Quantum condition the electron can be found somewhere).
for standing waves on an ‡ ȌZLWKWKHKHOSRI6FKU|GLQJHU䇻s equation,
orbit: allows calculation of electron energies. If the position of the electron is defined
‡ )RUDIUHHHOHFWURQȌLVDVLQHZDYHPRPHQWXP ('x is small) then the wavelength (pÆO)
LVSUHFLVHO\NQRZQS KȜEXWSRVLWLRQ[
entirely unknown (uncertainty principle!) will vary within a large scale :
 Paying tribute to the discoverers Summary: properties of the atom
(that will be emphasized in the course)

Stern-Gerlach experiment (1922) ± experimental proof for the spin states of the
electron 6WDUWLQJIURPÄVLPSOH´the atom ( simplification: composed of elementary particles)

ÄRUELWV´RIHOHFWURQVERXQGWRWKHQXFOHXV
electromagnet Screen
S schematics

- average distance of probability distribution functions

Ag-atom beam Silver beam M
L - each orbit means a discreat energy status of e-
splits in two
The net magnetic dipole momentum is - ./0«ODEHOVPHDQLQJQ 
determined by the 5s1 electron (angular N
momentum=0)

In an inhomogenous magnetic field, in addition to torque, net d~10-10 m Free

force arises on the magnetic dipoles: deviates the beam electron
Otto Stern (1888-1969) (QHUJ\PHDVXUHGLQÄH9´XQLWV

strong magnetic field

Energy states of bound electrons

H-atom

Walther Gerlach (1889-1979) Orbital electrons (-) Atomic nucleus

weak magnetic field
d<10-18 m Proton (+)
Neutron
The spin magnetic moment may have two values (+1/2, -1/2) Free electron
d~10-15 m
d~10-14 m

Atomic orbitals as charge distribution functions Æ

ÆChemistry

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X ± Z plane
䇾Spatial

1s
distribution
Good luck!
Bohr-radius

2s Thank you for your attention!

2p

Charge density versus distance from the nucleus

 Reminder: The
2S
sine/cosine function Y=A sin ( O x)
y Time period T Y=A sin ( 2S t)
O
T

Appendix:
t
Reminder: what a wave function is x

Reminder: Sinusoidal/Sine function Reminder: Cosine function

y y

T Zt Increasing the angle from 0 with constant speed

t=time
T Zt Increasing the angle from 0 with constant speed

one round T 2S , t T time period

S
ŸZ 2S 2S ˜ 1 2S ˜ f y=A  cos(Ȧt )=A ˜ sin(Zt  2 )
T T
y=A Â sin (Ȧt )
The phase angle *HQHUDOIRUPRIDÄZDYHIXQFWLRQ´VLQH-function of two variables:
t ±time and x - space coordinates
y

ĭ y A ˜ sin(2S t  2S x  M )
T O
Frequency (f):
t =0 f = 1/T (cycles/s, Hz) f (or Q)

Speed (c ) of energy propagation

ș ȦW  ĭ c = fāȜ (m/s)
or c = Ȝ/T

y=A Â sin (Ȧt + ĭ) A ± amplitude

Maximum of y