Title: Entropy, molecular motors, and non-thermal equilibrium statistical physics

Abstract: The transport of molecular cargos in neuronal cells is analyzed in the context of new developments in statistical physics. Our development of very bright optical probes enabled the long-term single tracking of molecular cargos in live neurons for tens of minutes. The number of dynein motors transporting a cargo was found to switch stochastically from one to up to five motors during the long-range transport in neurons. We are able to resolve individual molecular steps, and formulated a new, quantitative chemo-mechanical model where two ATP molecules are hydrolyzed sequentially. Our model is consistent with extensive structural, single-molecule and biochemical measurements.

The observed fluctuations in movement can be described by a steady-state non-thermal equilibrium effective temperature. The Fluctuation Theorem, first proved in 1993 and applicable in any non-thermal equilibrium processes, is shown to yield a minimum “uncertainty principle” limit, where the product of heat entropy and the statistical precision of any physical operation is greater than or equal to 2kBT. In the context of intercellular molecular transport, we show that a smaller variance in the movement of the cargo vesicle demands a greater expenditure of energy.