Some Bioengineering

Applications of Thermodynamics
Last week of class….

Or
 Recap of Some Bioengineering
Thermodynamics
• Material Properties of Lipid Membranes
– compressibility modulus, bending rigidity

• Domain Formation in Non-ideal

Membranes
– Cholesterol mixtures
 Outline for the Week
• Today: Cell Adhesion/Electromechanical
coupling

• Wed: Protein Folding/Electrochemistry

• Friday: Non-Equilibrium Thermodynamics

– Introduction to Transport
 Adhesion Molecules

Family Ligands recognized Stable cell junctions

Selectins Carbohydrates No
Integrins Extracellular matrix Focal adhesions and hemidesmosomes
Members of Ig superfamily No

Ig superfamily Integrins No
Homophilic interactions No

Cadherins Homophilic interactions Adherens junctions and desmosomes

Adhesion between leukocytes and endothelial cells Leukocytes leave
the circulation at sites of tissue inflammation by interacting with the
endothelial cells of capillary walls. The first step in this interaction is
the binding of leukocyte selectins to carbohydrate ligands on the
endothelial cell surface. This step is followed by more stable
interactions between leukocyte integrins and members of the Ig
superfamily (ICAMs) on endothelial cells.
• Specific molecules required for cell-cell or
cell-surface adhesion
– Implies a repulsive barrier normally exists that
must be overcome
 Thermodynamics of Cell Adhesion

Cells far apart Cells closer together Formation of cell-cell

Energy is sum of both Repulsive Interactions bridges counteracts
cells increase free energy repulsion – lowers free
energy

Free
Energy

0
 Simple Two-State Model
n1t = surface density of receptors on cell 1
n2t = surface density of receptors on cell 2

n1t = n1+nb
n2t = n2+nb

n1,2 is density of unattached receptors on respective cell

nb is surface density of cell bridges

nb=Nb/A where Nb is the absolute number of contacts

A is the area of contact
 Gibbs Energy of Adhesion
Consider process: cells go from separated state to a bound state
where formation of cell-cell bridges occur

∆G ( N b , A, s ) = ( N1t − N b ) µ1 (n1 ) + ( N 2t − N b ) µ 2 (n2 ) +

N b µ b (nb, s ) + AΓ( s )

First Two Terms:

Free energy change by unattached receptors on cell 1 and cell 2due to
bond formation
Third Term: free energy of the cell-cell bridges
Last Term: work done in overcoming nonspecific repulsion
Γ (s) represents free energy of non-specific repulsion
s is the separation distance
 Chemical Potential Terms
µ i (ni ) = µ io +k BT ln(ni )

µ b (nb ) = µ bo +k BT ln(nb )

µbo will vary because it depends on separation distance

spring model of a bond :

o o 1 2
µb (s) = µ b ( L) + κ ( s − L) +....
2
 Equilibrium Constant for Cell
Bridging

K (s) = ( o
exp [ µ1 o
+ µ2 o
− µb + k BT ] / k BT )
1 2
≈ K L [− κ ( s − L) ] / k BT ]
2
K(s) is maximum when separation distance equals
unstressed bond length
KL represents binding constant for formation of an
unstressed cell-cell bridge
Illustration of Spring Model
Forces Involved in Separation

γ
Γ( s ) = exp(− s / τ )
s
γ is the compressibility
τ is a characteristic distance
So now we have all the necessary terms in
the Gibbs Free Energy?

How do we determine the equilibrium

condition?
Phase Diagram for Adhesion
Equilibrium Depends on Number of
Receptors and Compressibilty
Effect of Changing KL
Agreement with Experiment
 Conclusions of the Model
• Bridging receptors concentrate in regions of
cell-cell contact
- experimentally observed
• Phase Transitions are observed in cell
adhesion
- cells are not billard balls
- adhesion can be stabilized by highly
cooperative interactions
“Who will lead me into that still more hidden and
dimmer region where Thought weds Fact, where
the mental operation of the mathematician and
the physical action of the molecules are seen in
their true relation? Does not the way pass
through the very den of the metaphysician,
strewed with the remains of former explorers?”

- James Clerk Maxwell, 1870

Adhesive Dynamics
 Kinetic Modeling

Reverse rate depends on force:

Here γ is the bond interaction

distance
Phase Diagram for Dynamic
Adhesion