title: Nonlinear cross-bridge elasticity and post-power-stroke events in fast skeletal muscle actomyosin.
abstract: Generation of force and movement by actomyosin cross-bridges is the molecular basis of muscle contraction, but generally accepted ideas about cross-bridge properties have recently been questioned. Of the utmost significance, evidence for nonlinear cross-bridge elasticity has been presented. We here investigate how this and other newly discovered or postulated phenomena would modify cross-bridge operation, with focus on post-power-stroke events. First, as an experimental basis, we present evidence for a hyperbolic [MgATP]-velocity relationship of heavy-meromyosin-propelled actin filaments in the in vitro motility assay using fast rabbit skeletal muscle myosin (28-29°C). As the hyperbolic [MgATP]-velocity relationship was not consistent with interhead cooperativity, we developed a cross-bridge model with independent myosin heads and strain-dependent interstate transition rates. The model, implemented with inclusion of MgATP-independent detachment from the rigor state, as suggested by previous single-molecule mechanics experiments, accounts well for the [MgATP]-velocity relationship if nonlinear cross-bridge elasticity is assumed, but not if linear cross-bridge elasticity is assumed. In addition, a better fit is obtained with load-independent than with load-dependent MgATP-induced detachment rate. We discuss our results in relation to previous data showing a nonhyperbolic [MgATP]-velocity relationship when actin filaments are propelled by myosin subfragment 1 or full-length myosin. We also consider the implications of our results for characterization of the cross-bridge elasticity in the filament lattice of muscle.
authors.affiliation: Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Persson
authors.forename: Elina
authors.initials: E
authors.lastname: Bengtsson
authors.forename: Lasse
authors.initials: L
authors.lastname: ten Siethoff
authors.forename: Alf
authors.initials: A
authors.lastname: Månsson
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D004548:Elasticity / Q000187:drug effects; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D015879:Myosin Subfragments / Q000378:metabolism; D017711:Nonlinear Dynamics; D011817:Rabbits
chemical_list: D015879:Myosin Subfragments; D000255:Adenosine Triphosphate; D000205:Actomyosin