title: Myosin cross-bridge mechanics: geometrical determinants for continuous sliding.
abstract: Advances in experimental techniques have provided new details on the molecular mechanisms governing the cross-bridge kinetics. Nevertheless, the issue of micromechanics of sliding is still debated. In particular, uncertainty exists regarding the myosin filament arrangement and structure and the mechanics of the myosin head with respect to the working stroke distance (WS) and the duty ratio (r), i.e. the fraction of the ATPase cycle time the myosin head is attached to the actin filament. The object of the present work is to provide a theoretical framework to correlate different features of cross-bridge mechanics; the main hypothesis is that the attachment between the actin filament and the surrounding myosin filaments has to be continuous through the sliding (continuous sliding hypothesis) in order to maximise the effect of the myosin head performance. A 3-D model of the sliding mechanism based on a geometrical approach is presented, which is able to identify the architectures that accomplish the continuous sliding under unloaded conditions. About 200 different configurations have been simulated by changing the myosin head binding range, i.e. its ability to reach an actin binding site from its rest position, WS, the myosin head orientation and the actin filament orientation. Only few configurations were consistent with the continuous sliding hypothesis. Depending on the parameter set adopted, the percentage of attached heads (%AH) calculated ranges between 4% and 28%, r between 0.08 and 0.02s(-1), and the sliding velocity between 0.7 and 10.6 microm/s. In all the cases, results were not affected by the WS value.
authors.affiliation: Dipartmento di Bioengegneria, Politecnico di Milano, Via Golgi 39, 21033 Milan, Italy. redaelli@biomed.polimi.it
authors.forename: A
authors.initials: A
authors.lastname: Redaelli
authors.forename: M
authors.initials: M
authors.lastname: Soncini
authors.forename: F M
authors.initials: FM
authors.lastname: Montevecchi
mesh_terms: D000199:Actins / Q000502:physiology; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009218:Myosins / Q000502:physiology*
chemical_list: D000199:Actins; D009218:Myosins