Modeling Coordinated Kinetics in Large Groups of Muscle Myosin Motors

Abstract

The kinetics of molecular motors are usually assessed for single or a few connected motors, or groups exceeding 100 motors. When we previously investigated coordinated kinetics of groups of 10 to 100 muscle myosin motors, we observed the emergence of group size-dependent patterns at the level of the whole motor group[1]. We used automated video analysis of in vitro motility assays, where fluorescent actin filaments were propelled by a surface coated with muscle myosins[2]. Here, actin motion showed two distinct modes: full arrest and phases of unidirectional sliding with a characteristic velocity[1]. The observation of either mode depended on the number of myosins maximally working as a coupled group on the same actin filament, which we calculated from myosin binding site distance (0.0355 µm) and filament length (L)[1]. Short actin filaments (L 1.0 µm) continuously slid forward[1]. We proposed a mathematical model, which monitors the coupled, load-dependent myosin kinetics at single myosin and single reaction resolution[1]. In the simulated myosin group kinetics, actin sliding and arrest corresponded to attractor-like-patterns “fixed point” and “limit cycle”, respectively; stochastic jumping between attractor-like-patterns explained sliding-arrest alternation[3]. We now extended this mathematical model by a spatial component: actin filament length is one spatial dimension, while myosin-to-myosin coupling is limited to ∼0.2 µm. In model simulations, arrested kinetics originated from both ends of the actin filament and could entrain global kinetics into arrest. Further, experimental velocity distributions recorded after addition of filamin crosslinker were reproduced, and explained by local perturbations by filamin crosslinking that spread to global extent along the filament. [1]Hilbert et al. Biophys J 2013 [2]Hilbert et al. PLoS Comp Biol 2013 [3]Hilbert et al. Biophys J 2015.