Monte Carlo simulation. (A) Cartoon illustrating interactions of myoVa motor molecules used for Monte Carlo simulation. (B) Representative trajectory of a 200-nm DPPC vesicle, indicating forces experienced by each actin-engaged motor (Upper, positive forces indicate resistive loads) and the spatial arrangement of each actin-engaged motor, as well as the vesicle center (Lower). The red dots indicate events where an attempted processive step was obstructed by the presence of another motor. (C) Cartoon illustrating the proposed mechanisms for enhanced vesicular transport velocity. Processive stepping of either attached motor (only lead motor stepping indicated in figure) results in net forward movement of the cargo. Intermotor forces cause an acceleration of detachment for the trailing motor. Upon trailing motor detachment, Brownian motion of the vesicle leads to a rapid recentering of the vesicle over the remaining bound motor(s), generating a net forward displacement (ΔX). As additional motors engage the track, the process is allowed to repeat. (D) Frequency of motor detachment relative to center position of the liposome. Motor detachment from the track is more frequent among trailing motors on fluid-state DOPC vesicles, whereas there is little detachment bias among leading and trailing motors on gel-state DPPC vesicles.