Hydrodynamics

• Hydrodynamics is the study of mechanics in a liquid, where

the frictional drag of the liquid cannot be ignored
• In Biology, there are two major problems
• First let‟s just consider fluid flow, where the fluid (e.g.,
water) is treated as continuous
• Can distinguish two types of flow: Steady (time independent)
and unsteady (time-dependent, also called turbulent)
• A special type of steady flow is laminar – or layered flow
• In biological fluids, viscosity becomes important
• The force imparted by the fluid is dependent upon its
viscosity
 Probability of transporting an ion inside a lipid vesicle
q
q q
V C   a
a V
Self Energy of the Capacitor
a 2 2
1 1 q q
CV  a 2 2 
2

2 2  a 2a
Energy change after transport
q 1 1 
2
E    
2a   l  w 
With  l  4,  w  80 the probability
 E
of transport of a single ion
across the lipid layer is  e RT  1020 i.e., impossible!!
 Viscous Force

Force
Area, S velocity, v

distance, l

Things get weird when viscosity increases

• Consider a cylinder containing corn syrup
• Add a dot of dye in corn syrup
• Stir the syrup/dye in one direction
• Reverse the direction of stirring
• The dot reforms
• Viscous fluids do not flow or mix
• No turbulence, no inertia
 Reynolds Number-the ratio of inertial to viscous forces

• Reynolds number=inertial force/viscous force

• =density (of medium), l=length, S=area, v/t=velocity over
time=acceleration, =viscosity (of medium)
• Inertial force is mass X acceleration = (density X volume) X (v/t)
• Viscous drag is viscosity X the velocity gradient
= (Viscous Force X area) X (v/l)

lSv / t lv
Re  Fi
Fv  S / t  
 What does it mean?
lv
R e 
• As size goes down, Re goes down
• As viscosity goes up, Re goes down
• At high Reynold‟s numbers- inertial forces dominate
• At low Reynold‟s numbers- viscous forces dominate
• Small objects in fluids are affected by the frictional
drag of the media to a great extent

Sample Reynolds’ numbers (EM Purcell)

• Bacterium swimming (organelle) 10-6
• Sperm swimming 10-2
• Fruit fly in flight 100
• Small bird flying 105
• Whale swimming 2x108
 Hydrodynamics at low Reynolds numbers

If the Reynolds number

, ,

one obtains the creeping flow equation.

human bacterium sinking cylinder

H2O:  = 0.001 Pa s;3

-5 -7
 = 1000 kg/m 6 v = 10 m/s v ~ 10 m/s
v = 1 m/s Re = 10 l =1 l =1
-5 -7
l =1m  Re = 10  Re = 10
 What does it mean?
• The forces associated with molecules of water interacting with each other
and solutes become relevant
• To a small molecule (bacteria) moving through a fluid is like you trying to
move in a highly viscous liquid. Imagine yourself living in asphalt (Berg
experiment)
– Being small is equivalent to being in a very viscous environment
• Water is highly ordered around you-you are the boundary layer
• surfaces nearby create boundary effects that alter the properties of water
significant distances away
• There is no inertia- if a bacteria stops swimming, it glides about the
distance of a hydrogen atom
• drag is irrelevant (shape is irrelevant) so streamlining is irrelevant

What does it mean to Cell Biology?

•A small predator cannot catch a prey by swimming at it, because it pushes the prey away as it swims
•A bacteria cannot swim by waving a flagella or cilia- it would return to the same place after a cycle of
motion
 Observation of the collective dynamics of WT S. marcescens 274 bacteria, swirling in a drop.

Rabani A, Ariel G, Be'er A (2013) Collective Motion of Spherical Bacteria. PLoS ONE 8(12): e83760. doi:10.1371/journal.pone.0083760
http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0083760
 Reynolds Number
• All macromolecules/bacteria/viruses are in the low R regime where
viscous forces dominate
• When modeling the flow of a fluid (water) around such a microscopic
object, it is important to consider the boundary layer of fluid near the
object – or, its hydration layer
• In physics, the two limits are “stick” and “slip” boundary conditions –
with stick conditions appropriate for macromolecules

MW < 2kDa MW >5 kDa

 Hydrodynamic Flow experiments

• A number of experimental techniques involve forcing

a macromolecule through a fluid (external force can
be electric, gravity, hydrodynamic, or even
magnetic)
• In this case we have:
Fnet  Fexternal  fu  ma
where f is the friction coefficient.
• After an extremely short time (~ ps), these two forces
balance and the acceleration goes to zero so that

Fexternal
Fnet  0 or u 
f
 Friction coefficient
• Stokes derived the friction coefficient for a sphere
(w/ stick BC):
f  6 R
where R is the sphere radius assuming
• “unstructured medium” (solvent molecules << sphere, mw> 5kDa)
• No inter-particle interaction
• Stokes relation for a „slipping‟ sphere: f = 4R
• For the rotational friction under „stick‟:  = 8V
• For a few other shaped objects there are close
expressions for f, but f for a sphere is the minimum
value for an equal volume (since f depends mostly on
surface area contact with the fluid and a sphere has
the minimum surface area for objects of the same
volume)
• Rods - f depends on L and axial ratio – Broersma
story
• There are now computer modeling programs that treat
any shaped object as a collection of spheres and can
calculate f
 The Shape of non Spherical Biological Molecules

The frictional coefficient of non-spherical molecules will in general

be large than that of a spherical molecule of the same volume,
simply because there will be a larger surface in contact with
solvent and this will of course increase the hydrodynamic drag. It
is possible to calculate frictional coefficient for any shape by
computational methods, and for certain simple shapes, the
calculation can be executed analytically
 The Shape of non Spherical Biological Molecules

In many cases, the shapes of rigid, non-spherical molecules can be

modeled in terms of some idealized shape. For example, virus
particles can be modeled as rods or ellipsoids of rotation.

We can use some simple consideration to calculate the frictional

coefficient for rod-like particles
 The Shape of non Spherical Biological Molecules
Suppose a rod-like particle has a length 2a and radius b. Its
volume is given by the formula:
Vrod  2ab 2

The axial ratio P is defined as:

P  a/b

For a rod-like particle, the frictional coefficient can be found to

be:

f  f0
2 / 31 / 3 P 2 / 3
ln( 2 P )  0.30
 The Shape of non Spherical Biological Molecules

The term f0 in the equation above is defined as

f 0  6R0

where R0 is defined as the radius of a sphere that has a volume

equal to the volume of the rod with axial ratio P=a/b, while the
remainder of the expression accounts for a „shape‟ correction, i.e.
represents the effect of the particular rod-like shape on diffusion
 The Shape of non Spherical Biological Molecules

R0 is determined as follows:

Vsphere  Vrod

4 3
R0  2ab 2
3

3ab 2
R 
3
0
2
 The Shape of non Spherical Biological Molecules

Another good example is the frictional coefficient for a prolate

ellipsoid (cigar-shaped particle):

The volume of a prolate ellipsoid is: 4 2

V pro  ab
3

where the lengths a and b are called the major and minor semi-
axis lengths
 The Shape of non Spherical Biological Molecules
For a prolate ellipsoid:
P 1 / 3 P 2  1
f  f0

ln P  P 2  1 
Where again: f 0  6R0
R0 is again the radius of a sphere which has a volume equal to the
volume of a prolate ellipsoid for which P=a/b

In this case: R0  ab 

2 1/ 3

The frictional coefficient ratio f/f0 for a

prolate ellipsoid does not vary markedly with
aspect ratio P. For example, for P ranging
from 1 to 20, f/f0 only varies from 1 to about 2
 Friction coefficient
• For asymmetrical particle  Ellipsoid of revolution

• Perrin Function
– As P increases F(p) changes slowly, whereas intrinsic viscosity changes
much more
– At same P, f for prolate ellipsoid > oblate ellipsoid of same volume
– f depends on two parameters: volume of an equivalent sphere and P
• For a circular cylinder with flat ends (e.g, DNA, TMV)

Where  is a function of P and depends on the “end effects”,

 = 0.386 as P  
 Bead

Shell

Platelet
 Concentration effects on f

• Stokes law is valid only in the limit of low

concentration where individual spheres do not “see”
each other
• At higher concentrations, flow “wakes” interact with
other spheres and increase the friction coefficient, so
that to a first approximation:

f  f o (1  kc)
 Hydration and Size of Biological Molecules
The radius of a spherical protein can be calculated from the
diffusion coefficient (i.e. the Stokes radius).
However, biological molecules are always hydrated and solvation
effectively increases the hydrodynamic volume of a molecule and
therefore its frictional coefficient.
Let us introduce the concept of partial specific volume, i.e. the
volume change in the solution when w2 grams of solute are added
(it expresses essentially the volume of solution occupied per gram
of un-hydrated solute, e.g. protein).  V 
V2   
 w2  T , P , w1

For an impenetrable object (e.g. glass bead), the partial specific

volume is simply the specific volume (volume per gram) of the
bead.
For biological molecule, it is found experimentally to depend on
conditions such as T, P, but also concentration of solute, pH etc.
 Hydration and Size of Biological Molecules

The hydrodynamic volume of an un-hydrated

molecule is simply the partial specific volume
multiplied by the weight per molecule. For an
hydrated protein or DNA molecule, we have to
include hydration as well and account for all
water molecules bound to the solute, which
effectively increase the size of the molecule as it
diffuses. The hydrodynamic volume can then be
calculated by adding the partial specific volume 1
to the volume of bound waters per gram of
macromolecule: d1 / 
 is the solvent density and d1 the number of grams of water
bound per gram of solute, typically 0.3-0.4 for proteins and 0.5-0.7
for DNA or RNA. Glycosylated proteins are also hydrated (0.5).
 Hydration and Size of Biological Molecules
To a good approximation, if it is assumed that there is a uniform
expansion, i.e., a particle of arbitrary shape of linear dimension l
is uniformly expanded by a constant factor h then:

such that then it follows that: which is

applicable for compact particles but not for elongated „rods‟.
From other experiments
it is now acceptable that
upon hydration a
particle gets a thick
uniform hydration
shell, which is usually 1
water molecule thick for
proteins.
 Hydration and Size of Biological Molecules

The degree of hydration of the protein (i.e. grams of hydrated

waters per gram of protein) may be determined by comparison of
the Stokes radius with the radius calculated assuming an un-
hydrated protein

If we define f0 as the frictional coefficient expected for an un-

hydrated molecule and f the frictional coefficient for a fully,
hydrated system, then:
3
 f  V2  d 1V1
  
 f0  V2

The denominator is the volume of an un-hydrated molecule, and

the term above is the total hydrodynamic volume, including
hydration