Assignment 2: Entropic diffusion of particles

(Due 29th August 9 am)

August 23, 2023

1 Introduction
We discussed that dominant forces at sub cellular scales are the thermal and
viscous in nature. We also discussed that one can easily neglect inertial forces
as compared to viscous forces. Since thermal effects direct molecules randomly,
their collective behaviour in a solution would depend upon the spatial distribu-
tion of their concentration.

2 Setup
We idealise cell to be a cubical domain of length l as shown in Fig. 1 and as-
sume that particle in consideration (protein molecules, ions or organelles) are
N in number, the temperature of the cell is T and the entire cell can be consid-
ered as an isolated system which does not exchange energy or particles from its
surrounding. We wish to obtain the governing dynamics this system while iden-
tifying forces emanating from thermal or entropic sources which compete against
the drag forces to allow for diffusion of proteins. We assume that molecules are
non-interacting and hence the system comprises of only kinetic energy of the
particles, which is proportional to the temperature (T ) of the medium.

3 Entropic Energy
For any system which does not exchange particles with its surrounding, one can
write the free energy (F) of that system as

F = E − TS (1)

where E is the internal energy stored in the system and S is the entropy. Free
energy is the amount of work that can be extracted from the system. Notice
that it is lesser than the amount of energy E stored by the system as both T
and S are restricted to be positive.

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Figure 1: (A)Representation of cell with diffusing particles, (B) Figure for prob-
lems in Section 5.1

Entropy (S) of the system is defined as a function of probability distribution

of arranging any given system in its W sub-states such that
XW
S = −kB (pi ln pi ) (2)
i=1

where kB is the Boltzmann constant, pi is the probability with which system

can be found in a given state i. It depends on the energy possessed by a given
sub-state (Ei ) as compared to rest of the states and is expressed as

e−Ei /kB T
pi = PW . (3)
−Ei /kB T
i=1 e

3.1 Questions
PW
1. Prove that i=1 pi = 1 and also that probability for individual states are
bounded such that 0 ≤ pi ≤ 1.
2. Prove that entropy (S) as defined through Eq. 2 is non negative.

Now for particles that are non-interacting, the energy stored by any given con-
figuration is equal to the kinetic energy stored by particles which is independent
of their arrangement and hence Eq. 2 can be written as

S = kB ln W. (4)

W being the number of states in which these particles can be arranged, should
be proportional to V N . Also, since the particles are identical, we will overcount
their arrangements by a factor of N ! to yield (For readers interested in the
historical development of this argument, please see Gibb’s paradox)

VN VN
W ∝ = C0 . (5)
N! N!

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The entropy hence is given by

VN
 
S = kB ln C0 (6)
N!

Using Stirling’s approximation (ln N ! ≈ N ln N − N for N ≫ 1) and substitut-

ing C0 = cN0 , we can rewrite the above equation as
   
c0 V
S = N kB ln +1 (7)
N

This means that free energy (F) excluding the fixed internal energy of the
system (E), can be written as
   
N
F = −T S = N kB T ln −1 (8)
c0 V

Till now we wrote the free energy for a discrete

P setPof particles, we can however
switch to a continuum by assuming N = Nj = cj ∆Vj and taking the limit
∆Vj → 0 to obtain free energy as
Z
F= kB T c [ln (c/c0 ) − 1] dV (9)
V

4 Entropic and Drag Forces

We wish to obtain the entropic force that would drive the motion of these
particles. This is not that straightforward and we will try to make an analogy
with a 1-D linear spring with stiffness k. If one gives it a velocity ẋ, then the
rate of change of energy is P = −(−kx)(ẋ) which is equal to force in the spring
(−kx) times the velocity.
We assume that particles are diffusing inside the cell with a velocity w and
using the analogy from the spring, we want to write the rate of change of free
energy as Z
∂F
= Ḟ = − (fe · w) dV (10)
∂t V
where fe would be the entropic force per unit volume on the particles. Taking
time derivative of Eq. 9 and assuming that the cell is not moving and hence any
subdomain of volume V is not changing with time, we obtain
Z Z
∂c
Ḟ = kB T ln (c/c0 ) dV = kB T ċ ln (c/c0 ) dV. (11)
V ∂t V

To resolve above equation in the form of Eq. 10, we need to relate the temporal
changes in concentration ċ to the diffusive velocity w of the particles. We do so
by taking an arbitrary volume V1 within R the cell, the total number of particles
within it at any given time is given by V1 c dV and it changes with time due to

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diffusion of particles going either out of the surface enclosing this volume (S1 )
and local unit normal to the surface (n), to allow us to write
Z Z
∂
c dV = − cw · n dS. (12)
∂t V1 S1

Using divergence theorem, we can convert the surface integral to that over the
volume to obtain Z Z
∂
c dV + ∇ · (cw) dV = 0. (13)
∂t V1 V1

Again, since domain V1 is not changing with time we obtain

Z
[ċ + ∇ · (cw)] dV = 0. (14)
V1

Since the choice of volumetric domain V1 is arbitrary, we can take it as small

as possible and can be taken anywhere inside the cell, we conclude that for the
integral to be zero, the integrand itself has to be zero at everywhere inside the
cell. This yields the balance or continuity equation for particles as

ċ + ∇ · (cw) = 0 ∀ x ∈ V. (15)

Here, ∇ · p signifies the divergence of vector field p and in cartesian co-ordinate

frame is written as ∇ · p = ∂px /∂x + ∂py /∂y + ∂pz /∂z. The above equation
is valid for every point within the volume domain V . Now we have a way to
relate ċ to the diffusive velocity w. Substituting above equation into Eq. 11, we
obtain Z
Ḟ = −kB T ∇ · (cw) ln (c/c0 ) dV. (16)
V
For any given vector field p and a scalar field q, we can write

(∇ · p) q = ∇ · (pq) − p · grad(q), (17)

where grad(q) is the gradient of scalar field q. Using the above relation we can
rewrite Eq. 16 as
Z Z
Ḟ = −kB T ∇ · [cw ln (c/c0 )] dV + kB T cw · grad [ln (c/c0 )] dV. (18)
V V

Using divergence theorem we can write the first integral on the RHS of the
above relation as
Z Z
Ḟ = −kB T cw · nS ln (c/c0 ) dS + kB T cw · grad [ln (c/c0 )] dV, (19)
S V

where nS is the unit normal to boundary surface of the cell (S). Since we assume
that number of particles within the cell is not changing, then we have cw·nS = 0

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on the boundary surface (S) . Thus, using grad [ln (c/c0 )] = grad(c)/c we can
obtain the rate of change of free energy as
Z
Ḟ = kB T grad(c) · w dV, (20)
V

On comparison with Eq. 10, we obtain the entropic force per unit volume as

fe = −kB T grad(c). (21)

This signifies that entropic forces will be against the gradient of concentration
of particles. The particles will also experience drag forces which will act against
their diffusing velocities and can be written as

fd = −γcw, (22)

where fd is drag force per unit volume and γ is drag coefficient. Assuming
particles to be spheres of radius r and viscosity of the fluid η, we can use
Stoke’s law to obtain γ = 6πηr.

5 Diffusion Equation
For equilibrium of particles at sub-cellular scales where inertial forces are not
that significant, we require drag forces to balance out the entropic forces and
hence obtain

fe + fd = 0 = kB T grad(c) + 6πηrcw ∀ x ∈ V. (23)

We take the divergence of the above equation and use continuity equation Eq. 15
to obtain the diffusion equation for particles as

kB T ∆c − 6πηrċ = 0, (24)

where ∆ is the Laplacian operator and for a scalar field q in cartesian co-ordinate
system
∂2q ∂2q ∂2q
∆q = 2
+ 2 + 2. (25)
∂x ∂y ∂z
We rearrange the diffusion equation to write

ċ = D∆c, (26)

where D = kB T /6πηr is the diffusion coefficient. Please note that above PDE
involves derivatives of concentration, both in time and space. Hence, to obtain
its solution, we need both initial and boundary conditions. The initial condition
will be the distribution of particles at t = 0 and boundary conditions would
require either imposing flux cw · n or concentration c.

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5.1 Questions
1. Write the diffusion equation in 1-D. Assuming particles are diffusing along
a slender chamber (representing a neuron) of length L as shown in Fig. 1,
write the corresponding boundary conditions which does not allow for flux
of particles through the chamber at both x = 0 and x = L.
2. Obtain the dimension of diffusion coefficient D. Comment about the time
scale of diffusion for particle starting to cover a distance L.
3. Estimate the time scales for diffusion of Na+ ion (r = 1Å) , protein
monomer (r = 5 nm) and organelles (r = 500 nm) to cover distances
of L = {50 nm, 10µm, 1m} in water with η = 10−3 Pa s.