Nanometer scale difference in myofilament lattice structure of muscle alter muscle function in a spatially explicit model

Abstract

Crossbridge binding and force in active muscle is dependent on the radial spacing between the thick and the thin filaments. This radial lattice spacing has been shown through spatially explicit modeling and experimental efforts to greatly affect isometric, force production in muscle. It has recently been suggested that this radial spacing might also be able to drive differences in mechanical function, or net work, under dynamic oscillations like those which occur in muscles in vivo. However, previous spatially explicit models either had no radial spacing dependence, meaning the lattice spacing could not be investigated, or did include radial spacing dependence but could not reproduce in vivo net work during dynamic oscillations and only investigated isometric contractions. Here we show the first spatially explicit model to include radial crossbridge dependence which can produce mechanical function similar to real muscle. Using this spatially explicit model of a half sarcomere, we show that when oscillated at strain amplitudes and frequencies like those in the hawk moth Manduca sexta, net work does depend on the lattice spacing. In addition, we can prescribe a trajectory of lattice spacing changes in the spatially explicit half sarcomere model and investigate the extent to which the time course of lattice spacing changes can affect mechanical function. We simulated a half sarcomere undergoing dynamic oscillations and prescribed the Poisson's ratio of the lattice to be either 0 (constant lattice spacing) or 0.5 (isovolumetric lattice spacing changes). We also simulated net work using lattice spacing data taken from Manduca sexta which has a variable Poisson's ratio. Our simulation indicates that the lattice spacing can change the mechanical function of muscle, and that in some cases a 1 nm difference can switch the net work of the half sarcomere model from motor like to brake like.