Stochastic Force Generation in an Isometric Binary Mechanical System: A Thermodynamic Model of Muscle Force Generation

Abstract

With implications for both clean energy technologies and human health, models of muscle contraction provide insights into the inner workings of one of the most energy efficient engines on the planet and into the modifications to that engine that lead to human diseases. However, only scientific methods can provide these insights. A binary mechanical model is a recently developed thermodynamic model of muscle contraction that implies a novel entropic kinetic formalism, provides a solution to a paradox that has perplexed scientists for over a century, and accounts for many mechanical and energetic aspects of muscle contraction. Here we use this model to perform discrete state chemical simulations of isometric force generation under different conditions and show explicitly that force generating kinetics are bounded by thermodynamic equations, that four phases of force generation occur as four separate thermodynamic processes, and that periodic force generation emerges with amplitudes and ergodicities that bifurcate between constant and stochastic values through mechanisms easily understood relative to ideal thermodynamic processes. We discuss these results relative to experimental observations of spontaneous oscillatory contractions (SPOCs) in muscle and periodic force generation in small myosin ensembles.

The Problem with Inventing Molecular Mechanisms to Fit Thermodynamic Equations of Muscle

“…All phases are well-defined combinations of two explicit thermodynamic processes [15,37,38] System entropy 0 -k B Tln[(N bound + 1)/N unbound ] [15,19,28] Thermal Energy Heat content of molecules Heat content of system * While under certain conditions, N bound increases with binding energy. In general, none of the above corpuscular mechanisms are supported experimentally.…”