Microscopic reversibility: the organizing principle for design, characterization, and operation of molecular machines

R. Dean Astumian Dept. of Physics University of Maine

Plenty of room at the bottom

Feynmans challenge: Build a motor less than 1/64th of an Inch on a side. Accomplished by William McClellan less Than a year later a tour de force of miniaturization At equilibrium (without power) the motor doesnt move-The challenge: How to use energy to cause directed motion?

50000 time smaller!

Equilibrium maintained dynamically

Every motion present at equilibrium The challenge: How to use energy to prevent unwanted motion
One microscopic picture to keep in mind here is that of a nanoscale machine, intermittently experiencing sudden violent 80 pN nm (~20 kBT) kicks originating from ATP hydrolysis.??? Liphardt, Nature Physics 8: 638-639 (2012)

Microscopic reversibility as the operating principle of molecular machines Nature Nanotechnology, 7: 684-688 (2012)
Biological motors and pumps are equilibrium devices that couple chemical, electrical and mechanical processes in an environment that is far from equilibrium. Recognition of the key role played by microscopic reversibility in their operation is a step towards rational design of artificial molecular devices.

What is equilibrium?

It is somewhat disappointing that more recent discussions of the laws of thermodynamics contain no relevant reference to the investigations of Boltzmann and Smoluchowski. The absence of references, particularly to Smoluchowski, is to be deplored since no one has contributed so much as Smoluchowski to a real clarification of the issues involved. Suresh Chandrasekhar, RMP, 1943.

Smoluchowski, Marian. (1914). Limits on the Validity of the Second Law of Thermodynamics

The overdamped equation of motion From which we obtain the probability distribution for Distance travelled in time, t.

From the ratio and from the Stokes-Einstein relation we get the barometric formula from single particle trajectories

The unreasonable effectiveness of equilibrium theory for interpreting Nonequilibrium experiments, R. D. Astumian AJP 74: 683-688 (2006)

Experimental Demonstration of Violations of the Second Law of Thermodynamics for Small Systems and Short Time Scales

Velocity and position relaxation times

Simple transform substitute into the equation of motion to get Which, in the over-damped limit becomes
Lars Onsager

the Orenstein-Uhlenbeck process, the Solution to which was given by Onsager And Machlup in 1953.

Equilibrium theory for a particle pulled by a moving optical trap, RDA, JCP 126: 111102 (2007)

As before, this cleans up nicely when we take the ratio

where and

is the avg. force is the displacement

The equilibrium distribution is So we find the generalized detailed balance condition

Drag force at velocity of 1.25 micron/s is appx. 10-14 N i.e., less than gravity on a 1 micron particle in water! Work distribution function:

Ratio is very simple

Probability of negative work

Onsager-Machlup Theory for time dependent potentials

The essential physical assumption about the irreversible processes is that they are linear, i.e., that the fluxes depend linearly on the forces that cause them.

Lars Onsager

where

is the gradient of

Optimal modulation of a Brownian Ratchet and enhanced Sensitivity to a weak external force, M. Tarlie and RDA, PNAS 95: 2039-2043 (1998).

The noise is Gaussian

Using the Gaussian noise as a proper gator we get an expression for the probability of a trajectory in a space
with

Principle of Microscopic Reversibility

and

The ratio of the probabilities of any trajectory and its microscopic reverse is the exponential of the work done by any external forces (time dependent or not) and the change in potential energy of the system.

Corollaries of Microscopic Reversibility

Binding/Dissociation of oxygen to myoglobin

Binding - Local to global

Dissociation - Local to global?

PNAS 82: 5000-5004, 1985

Consistent with Macroscopic Experience

IUPAC Gold Book:

Microscopic Reversibility - In a reversible reaction the mechanism in one direction is exactly the reverse of the mechanism in the other direction. This does not apply to reactions that begin with photo-excitation

Life at Low Reynolds number - E. M. Purcell, AJP 45: 3-11 (1977)

A simple molecular walker

A dimeric motor A polymeric track
Chemical fuel An opposing force

Kinetic Diagram

Graphical Approach
Forward stepping SP Backward stepping SP

or
Chemistry with no stepping

or
Stepping with no chemistry

Process

Constraint of MR

Forward stepping SP

Backward stepping SP or Chemistry with no stepping or Stepping with no chemistry

RDA, Ann. Rev. Biophysics, 40:289-313 (2011)

Allosteric Interaction Natures own Mechanism for a Maxwells Demon

Astumian and Derenyi, Euro. Biophys. Journ. 27: 474-489 (1998).

Microscopic reversibility as the operating principle of molecular machines Nature Nanotechnology, 7: 684-688 (2012)
Biological motors and pumps are equilibrium devices that couple chemical, electrical and mechanical processes in an environment that is far from equilibrium. Recognition of the key role played by microscopic reversibility in their operation is a step towards rational design of artificial molecular devices.

Acknowledgements
I am very grateful to the German Humboldt Foundation for having facilitated this work by conferral of a Humboldt Research Award, and to my colleagues in Munich - Hermann Gaub, Dieter Braun, and Jan Neumann for wonderful discussions over excellent beer, I am also grateful to Fraser Stoddart, David Leigh, Bartosz Gryzbowski, Ali Coskun, and Ayusman Sen for inspiring discussions about chemical implementation of molecular machines.