Thermal forces and Diffusion

Thermal motion
Important for molecular and cellular mechanics

•Chemical reaction driving biological processes have

energies that are only a little higher
•Diffusive motion is large compared to directed motion
•Thermal motion is necessary to reach transition state
•Molecular machines operate in a noisy diffusive
environment
Focus Questions
• Why is the nanoworld different from the
macroworld?
Thermal motion of molecules!

• If motion of molecules is random how can we

say anything predictive about what is going
on?
Collective action of many randomly moving
actors can be effectively predicted, even if the
individual motions can not!
Brownian Motion

0.8 µm latex beads

Peter Brown 1827
– 1 µm Pollen
• No life-non stop motion and all similarly sized
objects (soot, dust, ground up sphinx) show the
same motion.
=> colloidal particles

molecular collisions!
Brownian motion
• Collisions with water and other molecules result in a
change of momentum in the fluid-impulsive force on
colliding object
• Collisional forces are called thermal forces
amplitude~T
movement=thermal motion
• Thermal forces are randomly directed-frequent change
of direction =>Diffusion
• For a free particle in solution this diffusion is called
Brownian motion
How fast do they move?

Molecule hits wall

Momentum change mvx to –mvx
=> 2mvx delivered to wall
Round trip δt=2L/vx
N molecules

=> rate of delivery of momentum f=(2mvx)(vx/(2L))N=mvx2N/L

Force/Area
p = m v x2 N / V
m v x2 = kbT
Ideal gas law: pV=NkbT
e.g. a Protein: 14000 g/mol
⇒1 Molecule m=2.3 10-23 kg
⇒kBT=4 10-21J
⇒<vx2>1/2=13 m/s
 m v x2 = kbT True for all directions!

Particle with mass m has energy kBT per degree of

freedom (direction)

2
v 2 = 3 vx
1 1 1
* m v 2 = kbT
2 3 2

The average kinetic energy of a molecule in an

ideal gas is 3/2 kbT

Velocity of each individual molecule unknown

Boltzmann distribution
•kbT = 4.1*10-21 J =4.1 pN nm
•kbT = 2.5 kJ/mol
•kbT = 25 meV
Boltzmann‘s law
• In thermodynamic equilibrium particles tend towards their lowest
energy state.
• Agitation my molecular collisions causes the molecules to spend a
fraction of their time in states with higher energy.
• Boltzmann‘s law gives the probability pi that a particle in thermal
equilibrium can be found in a state i that has energy Ui
p2  ∆U i 
= exp − 
1  Ui  2 states p1 k
 B T
pi = exp − 
Z k
 B T

Partition-Function
 U 
Z = ∑i exp − i 
 k BT 
Boltzmann constant
kB = 1.38 x 10-23J/K
=> Thermal Energy at 25°C: kBT = 4 x 10-21J
Brownian Motion

0.8 µm latex beads

Peter Brown 1827
1 µm Pollen
• No life-non stop motion and all similarly sized
objects (soot, dust, ground up sphinx) show the
same motion.
=> colloidal particles
molecular collisions!

1) why visible and much larger than atoms?

2) v~10-100 m/sec; d(H20)~1nm (close packing)

=> Motion < 1nm before collision!!!

=> Collision rate : 103m/s/10-9m~1012 collisions/sec
=> Monitored with only 30/sec!!!

????? Situation: 1905

Einsteins Idea:

Both problems cancel each other:

• We only see the rare big events
– e.g. Tower + Chessboard
• Random walk has structure on all length
scales
 The Nobel Prize in Physics 1921
"for his services to Theoretical Physics, and
especially for his discovery of the law of the
photoelectric effect“
3 papers in 1905:
March: Photoelectric effect
May: Brownian motion
June: special theory of relativity

1926:
Investigations on Theory of Brownian Movement
Presentation Speech for the Nobel Prize 1921

....
Throughout the first decade of this century the so-called Brownian
movement stimulated the keenest interest. In 1905 Einstein
founded a kinetic theory to account for this movement by means of
which he derived the chief properties of suspensions, i.e. liquids
with solid particles suspended in them. This theory, based on
classical mechanics, helps to explain the behaviour of what are
known as colloidal solutions, a behaviour which has been studied
by Svedberg (1926), Perrin (1926), Zsigmondy (1925) and
countless other scientists within the context of what has grown into
a large branch of science, colloid chemistry.

....
Brownian motion
All particles i at t=0 are at x=0

the following rules hold: δ = ± vxτ

• Every particle makes a step δ to the left or right every
τ seconds
• Probability for left or right is equal (=1/2), no memory,
independent, no bias
• All particles move independent from the others, they
do not interact
N particles
i-th particle after n steps:

On average: +: one half -: the other half

mean displacement after the
nth step
averaged over all particles N:
N

∑ ±δ = 0
i =1

⇒ x(n) = x(0) = 0
 ⇒ x(n) = x(0) = 0
On average the particles do not move away
But the distribution becomes broader!!
 2. Moment:

Average over all particles N:

=0
 x 2 (n) = x 2 (n − 1) + δ 2

xi (0) = 0 For all particles i

⇒ x 2 (0) = 0 ⇒ x 2 (1) = δ 2

⇒ x 2 (2) = 2δ 2

⇒ x 2 (n) = nδ 2
 ⇒ x 2 (n) = nδ 2

t = nτ

Distribution broadens with t1/2

 = 2D
D: Diffusion coefficient

[D]= length2/time
Structure on all length scales
studied length scale x>>δ
=> wait longer than x2/2D!!
In 2D:
x2+y2 while independent

In 3D:
x2+y2 +z2 while independent
Can diffusion be used as a cellular transport mechanism?

(7 h) (8 years)
D~2000 µm2/s

(6 days) (150 years)

D~100 µm2/s

(3 years) (30000 years)

D~0.5 µm2/s
 Diffusion in cellular transport?

• Diffusion of proteins becomes slow over Eukaryotic cells are

distances greater than ~ 100 µm usually smaller!

• Organelles are almost immobile Active transport

(cytoskeleton obstructs movement required
effective D smaller in cells)

• For highly elongated cells (e.g. neurons)

active transport is essential even for
small molecules
Active transport
• http://www.garlandscience.com/textbooks/0815341636/resources/videos/files/Fig
_13.05.mov
Diffusion in Membranes
 Typ D

Typ C

Typ A
One can not define a velocity for diffusion; it depends
on the observation time!!

= vapp

The smaller t, the higher the velocity!!!

For t< τ the apparent velocity v app would be
larger than the instantaneous velocity δ/τ = v !!!

δ2
2D =
τ
Friction
• Diffusion results from f
random collisions
• Friction? x

Gravity f=mg
Terminal velocity determined by friction-what is the origin of this friction?
Collisions once per δt 1 f
∆x = v x (0)∆t + (∆t ) 2
Newton dvx/dt = f/m 2m
vx(t) = vx(0) + ft/m
1 f
No memory v x (0) = 0 ∆x = (∆t ) 2
2m
random collisions-drift velocity

friction coefficient ζ = 2m / ∆t vdrift = f / ζ

Stokes
For spherical objects:

ζ = 6πηR

η = viscosity of fluid (water-10-3 kgm-1s-1 at T=20°C)

R = radius of the particle
Einstein
Friction coefficient ζ = 2m / ∆t L and ∆t are
2
molecular-scale
Diffusion coefficient D = L /(2∆t ) parameters

( L / ∆t ) 2 = (v x ,o ) 2
2 3 equations 2 unknowns
v x = k bT / m

Relation between D and ζ Dζ = kbT

Einstein relation
For spherical objects:

k BT k BT
D= =
ζ 6πηR

Fluctuation and dissipation are coupled

kb can be determined from a macroscopic measurement
t+τ: Flux Jx in x-Direction??
½ of the particles at x over dotted line went to the right
½ of the particles at x+δ went over the dotted line to the left

=> the net-number of

particles going to the right:
 Flux =number of particles per unit area and time

∗δ 2 / δ 2

Number per volume

= concentration

δ →0 1. Fick
If no gradient is present => J=0 -> equilibrium
What is driving the flux?

Flux is driven by the probability of hopping

=> Entropic force
 Particles are not
created or destroyed!

Volume of the box: V = Aδ

During time interval τ: J(x)Aτ Particles from left

J(x+δ)Aτ Particles to the right

Number of particles per unit volume changes with the rate:

 τ → 0, δ → 0

1. Fick
2. Fick

Diffusion equation
 Solving the diffusion equation

c(0) = c0
c(L) = 0
L

Quasi steady state dc/dt = 0 c

c(x) = c(0)(1 - x/L)
d2c/dx2 = 0

x
Diffusion through membrane
 Diffusion through membrane
Flux through membrane Js = -Ps∆c
Permeability Ps

R= 10 µm
Ps= 20 µms-1

R
cin = N(t)/V, V = 4/3πR3
Js = -Ps(cout-cin(t)) = -Ps∆c
dN/dt = -Ajs
relaxation of d(∆c)/dt = (APs /V)∆c
concentration
∆c = ∆c(0)e-t/τ
jump
τ = V/PsA ~0.2 s
t=1, ∆c=0.007∆c(0)
Diffusion through membrane
Flux through membrane Js = -Ps∆c
Simplified => pores are formed
Fraction α of the surface contains pores

dN/dt = -αAjs

Js = -αPs∆c

Pore
 O2 O2
O2
O2
O2

O2 O2
= bacterium, radius R

Oxygen concentration c(r)

r
Lake is huge steady state dc/dt = 0
c(∞) = c0 c( R ) = 0

O2 does not accumulate J 4πr 2 = I c(r ) = c0 (1 − ( R / r ))

c(r ) = A − (1 / r )( I /( 4πD ))
A = c0
I = 4πDRc0
 O2 O2
Oxygen uptake O2
O2
I = 4πDRc0 O2

O2 O2

r
Uptake ~ R
size limitation
Consumption ~ Volume ~ R3
Solutions:

• Compartmentalization
• Active transport
• Surface protrusions

microvilli
FRAP

Bron: Reits et al 2001

Diffusion

chemoreception

Filament growth
• Why is the nanoworld different from the
macroworld?
Thermal motion of molecules!

• If motion of molecules is random how can we

say anything predictive about what is going
on?
Collective action of many randomly moving
actors can be effectively predicted, even if the
individual motions can not!
End
Partition Coefficient

Ps=BD/L

B=partition coefficient