Spatially explicit, nano-mechanical models of the muscle half-sarcomere: Implications for biomechanical tuning in atrophy and fatigue

Astronaut biomechanical performance depends on a wide variety of factors. Results from computational modelling suggest that muscle function-a key component of performance-could be modulated by compliance of the contractile filaments in muscle, especially when force is low such as transient Ca2+ activation in a twitch, reduced activation in muscle fatigue encountered during EVA, or perhaps atrophy during prolonged space flight. We used Monte-Carlo models to investigate the hypotheses that myofilament compliance influences muscle function during a twitch, and also modulates the effects of cooperative interactions between contractile proteins on force generation. Peak twitch force and the kinetics of force decay were both decreased, while tension cost was increased, when myofilament compliance was increased relative to physiological values. Both the apparent Ca2+ sensitivity and cooperativity of activation of steady-state isometric force were altered by myofilament compliance even when there were no explicit interactions included between binding sites. The effects of cooperative interactions between adjacent regulatory units were found to be greater than either the effect of myofilament compliance on apparent cooperativity of activation or that due to myosin cross-bridge-induced cooperativity. These results indicate that muscle function may be “tuned” at the molecular level, particularly under conditions of reduced Ca2+ activation.