The Transient Mechanics of Muscle Require Only a Single Force-Producing Cross-Bridge State and a 100 Å Working Stroke.

Abstract

Simple SummaryWith modern increased computational power, newly developed computer programs can be used to simulate how muscle contracts. Here, we created, in silico, a “virtual” muscle that includes modelled myosin cross-bridges, and, using statistical mechanical methods, we calculated the macroscopic response of the muscle during contraction and as a result of applied transients. Good fits to many experimental observations were obtained with this simple model with one attached force-producing state and using a single cross-bridge step size of 100 Å.An informative probe of myosin cross-bridge behaviour in active muscle is a mechanical transient experiment where, for example, a fully active muscle initially held at constant length is suddenly shortened to a new fixed length, providing a force transient, or has its load suddenly reduced, providing a length transient. We describe the simplest cross-bridge mechanical cycle we could find to model these transients. We show using the statistical mechanics of 50,000 cross-bridges that a simple cycle with two actin-attached cross-bridge states, one producing no force and the other producing force, will explain much of what has been observed experimentally, and we discuss the implications of this modelling for our understanding of how muscle works. We show that this same simple model will explain, reasonably well, the isotonic mechanical and X-ray transients under different loads observed by Reconditi et al. (2004, Nature 428, 578) and that there is no need to invoke different cross-bridge step sizes under these different conditions; a step size of 100 Å works well for all loads. We do not claim that this model provides a total mechanical explanation of how muscle works. However, we do suggest that only if there are other observations that cannot be explained by this simple model should something more complicated be considered.