title: Filament compliance effects can explain tension overshoots during force development.
abstract: Spatially explicit stochastic simulations of myosin S1 heads attaching to a single actin filament were used to investigate the process of force development in contracting muscle. Filament compliance effects were incorporated by adjusting the spacing between adjacent actin binding sites and adjacent myosin heads in response to cross-bridge attachment/detachment events. Appropriate model parameters were determined by multi-dimensional optimization and used to simulate force development records corresponding to different levels of Ca(2+) activation. Simulations in which the spacing between both adjacent actin binding sites and adjacent myosin S1 heads changed by approximately 0.06 nm after cross-bridge attachment/detachment events 1), exhibited tension overshoots with a Ca(2+) dependence similar to that measured experimentally and 2), mimicked the observed k(tr)-relative tension relationship without invoking a Ca(2+)-dependent increase in the rate of cross-bridge state transitions. Tension did not overshoot its steady-state value in control simulations modeling rigid thick and thin filaments with otherwise identical parameters. These results underline the importance of filament geometry and actin binding site availability in quantitative theories of muscle contraction.
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, KY 40536-0298, USA. k.s.campbell@uky.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Campbell
mesh_terms: D000199:Actins / Q000737:chemistry; D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D001703:Biophysics / Q000379:methods*; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008962:Models, Theoretical; D009010:Monte Carlo Method; D018482:Muscle, Skeletal / Q000378:metabolism; D015879:Myosin Subfragments / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D012518:Sarcomeres / Q000737:chemistry
chemical_list: D000199:Actins; D015879:Myosin Subfragments; D009218:Myosins; D002118:Calcium