Huxley’s model for muscle contraction revisited: The importance of microscopic reversibility

Abstract

Andrew Huxley’s model for muscle contraction is the first mechanistic description of how an energy-providing chemical reaction, ATP hydrolysis, can be coupled by a molecule (myosin) to do work in the environment in a cyclic process. The model was originally used to fit experimentally obtained force vs velocity curves, and has served as a paradigm for understanding mechanochemical coupling ever since. Despite the remarkable success in fitting kinetic data, Huxley’s model is thermodynamically inconsistent in several regards, most notably in its failure to include thermal noise in the description of the mechanical transitions by which motion occurs. This inconsistency has led subsequent workers to incorrect conclusions regarding the importance of mechanical transitions for determining the direction of motion, the efficiency of energy conversion, the ratio of forward to backward steps, and the applied force necessary to stop the motion of chemically driven molecular motors. In this chapter an extension of Huxley’s model is described where the principle of microscopic reversibility provides a framework for developing a thermodynamically consistent description of a molecular machine. The results show clearly that mechanical strain and the so-called “power stroke” are irrelevant for determining the directionality and thermodynamic properties of any chemically driven molecular motor. Instead these properties are controlled entirely by the chemical specificity that describes how the relative rates of the ATP hydrolysis reaction depend, by allosteric interactions, on the mechanical state of the molecule. This mechanism has been termed an “information ratchet” in the literature. In contrast to the results for chemical driving, a power stroke can be a key component for the operation of an optically driven motor, the transitions of which do not obey microscopic reversibility.