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Chemomechanical regulation of myosin-1c crossbridges

Myosin-1c is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by a hair cell, the sensory receptor of the inner ear. In this context myosin molecules operate neither as filaments, as occurs in muscles, nor as single molecules, as characterizes intracellular transport. Instead, myosin-1c molecules occur in a cluster in which they may exhibit cooperative properties. To better understand the motor's function, we introduce a theoretical description of myosin-1c's chemomechanical cycle based on experimental data from recent single-molecule studies. The cycle consists of distinct chemical states that the myosin molecule stochastically occupies. We explicitly calculate the probabilities of the occupancy of these states and show their dependence on the external force, the availability of actin, and the nucleotide concentrations as required by thermodynamic constraints. This analysis highlights that the strong binding of myosin-1c to actin is dominated by the ADP state for small external forces and by the ATP state for large forces. Our approach shows how specific parameter values of the chemomechanical cycle for myosin-1c result in behaviors distinct from those of other members of the myosin family. Integrating this single-molecule cycle into a simplified ensemble description, we predict that the average number of bound myosin heads is regulated by the external force and nucleotide concentrations. The elastic properties of such an ensemble are determined by the average number of myosin cross-bridges. Changing the binding probabilities and myosin's stiffness under a constant force results in a mechanical relaxation which is large enough to account for fast adaptation in hair cells.

 

 

 Myosin-1c

A schematic drawing depicts the simplified reaction cycle of myosin-1c. Transitions between the states occur upon the binding and release of nucleotides or upon myosin's attaching to or detaching from an actin filament. The unbound or weakly bound states are shown with a blue background.

Myosin-1c is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by a hair cell, the sensory receptor of the inner ear. I