Thermodynamics and Kinetics of a Binary Mechanical System: Mechanisms of Muscle Contraction

Abstract

Biological motors function at the interface of biology, physics, and chemistry, and it remains unsettled what rules from which disciplines account for how these motors work. Myosin motors are enzymes that catalyze the hydrolysis of ATP through a mechanism involving a switch-like myosin structural change (a lever arm rotation) induced by actin binding that generates a small displacement of an actin filament. In muscle, individual myosin motors are widely assumed to function as molecular machines having mechanical properties that resemble those of muscle. In a fundamental departure from this perspective, here, I show that muscle more closely resembles a heat engine with mechanical properties that emerge from the thermodynamics of a myosin motor ensemble. The transformative impact of thermodynamics on our understanding of how a heat engine works guides a parallel transformation in our understanding of how muscle works. I consider the simplest possible model of force generation: a binary mechanical system. I develop the mechanics, energetics, and kinetics of this system and show that a single binding reaction generates force when muscle is held at a fixed length and performs work when muscle is allowed to shorten. This creates a network of thermodynamic binding pathways that resembles many of the characteristic mechanical and energetic behaviors of muscle including the muscle force-velocity relationship, heat output by shortening muscle, four phases of a muscle tension transient, spontaneous oscillatory contractions, and force redevelopment. Analogous to the thermodynamic (Carnot) cycle for a heat engine, isothermal and adiabatic binding and detachment reactions create a thermodynamic cycle for muscle that resembles cardiac pressure-volume loops (i.e., how the heart works). This paper provides an outline for how to re-interpret muscle mechanic data using thermodynamics - an ongoing effort that will continue providing novel insights into how muscle and molecular motors work.