An elastically tethered viscous load imposes a regular gait on the motion of myosin-V. Simulation of the effect of transient force relaxation on a stochastic process

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Abstract
Myosin-V is a processive molecular motor that moves membrane vesicles along actin tracks. In the simple model for motor and cargo motion investigated here, an elastic connection between motor and cargo transiently absorbs the abrupt mechanical transitions of the motor, and allows smooth relaxation of the cargo to a new position. We use a stochastic description to model motor stepping, with kinetics that depends on the instantaneous force exerted on the motor through the elastic connection. Tether relaxation is modelled as a continuous process, in which the rate is determined by the viscous drag of the cargo and the stiffness profile of the connection. Quantitative combined stochastic-continuous simulation of the dynamics of this system shows that bulky loads can impose a highly regular gait on the motor. If the characteristics of the elastic connection are similar to those of the myosin-II coiled-coil domain, the myosin-V motor, tether and cargo form a true escapement, in which the motor only escapes from its current position after one or more force thresholds have been crossed. Multiple thresholds limit the variation in tether length to values below that of the total step size.