Purpose:The aim of this study was to extend current half-sarcomere models by involving a recently found force-mediated activation of the thick filament and analyze the effect of this mechanosensing regulation on the l...Purpose:The aim of this study was to extend current half-sarcomere models by involving a recently found force-mediated activation of the thick filament and analyze the effect of this mechanosensing regulation on the length stability of half-sarcomeres arranged in series.Methods:We included a super-relaxed state of myosin motors and its force-dependent activation in a conventional cross-bridge model.We simulated active stretches of a sarcomere consisting of 2 non-uniform half-sarcomeres on the descending limb of the force-length relationship.Results:The mechanosensing model predicts that,in a passive sarcomere on the descending limb of the force-length relationship,the longer half-sarcomere has a higher fraction of myosin motors in the on-state than the shorter half-sarcomere.The difference in the number of myosin motors in the on-state ensures that upon calcium-mediated thin filament activation,the force-dependent thick filament activation keeps differences in active force within 20%during an active stretch.In the classical cross-bridge model,the corresponding difference exceeds 80%,leading to great length instabilities.Conclusion:Our simulations suggest that,in contrast to the classical cross-bridge model,the mechanosensing regulation is able to stabilize a system of non-uniform half-sarcomeres arranged in series on the descending limb of the force-length relationship.展开更多
文摘Purpose:The aim of this study was to extend current half-sarcomere models by involving a recently found force-mediated activation of the thick filament and analyze the effect of this mechanosensing regulation on the length stability of half-sarcomeres arranged in series.Methods:We included a super-relaxed state of myosin motors and its force-dependent activation in a conventional cross-bridge model.We simulated active stretches of a sarcomere consisting of 2 non-uniform half-sarcomeres on the descending limb of the force-length relationship.Results:The mechanosensing model predicts that,in a passive sarcomere on the descending limb of the force-length relationship,the longer half-sarcomere has a higher fraction of myosin motors in the on-state than the shorter half-sarcomere.The difference in the number of myosin motors in the on-state ensures that upon calcium-mediated thin filament activation,the force-dependent thick filament activation keeps differences in active force within 20%during an active stretch.In the classical cross-bridge model,the corresponding difference exceeds 80%,leading to great length instabilities.Conclusion:Our simulations suggest that,in contrast to the classical cross-bridge model,the mechanosensing regulation is able to stabilize a system of non-uniform half-sarcomeres arranged in series on the descending limb of the force-length relationship.
