Myosin Motor Dynamics in Filopodia

Abstract

ATP-driven molecular motors are ubiquitously used for various cellular transport processes. Myosin motors that walk on actin filaments have been detected in both filopodia and stereocilia. Myosin X plays an important role in filopodial formation and growth, however, the specific mechanisms and cargo of various myosins remain unclear. To address these issues, we have developed a comprehensive stochastic computational model of a filopodium, incorporating active transport by motors. Our model indicates that efficient motor mediated transport is hindered by sequestration of G-actin cargo by motors, as well as clogging of the actin filaments by multiple motors. Our work suggests potential mechanisms for overcoming these transport bottlenecks. Furthermore, experimentally measured motor concentration profiles along the filopodial tube are difficult to explain. This motivated us to look into the details of this distribution. We created a theoretical model describing the steady-state concentration profile of the motors and compared it with the computer simulations. The theoretical results semi-quantitatevly agree with the numerical data. In the stationary state, the model shows a quick saturation of actin filaments with walking motors as a function of distance from the filopodial base. This adversely affects the flux of motors and their cargo to the filopodial tip, as space for motors to step into runs out. Thus, the clogging problem is at least as important as the sequestration one, and the cell would probably need to employ special facilities for solving it in order to achieve efficient active transport, and thus longer filopodia.