Stochastic models of polymerization-based axonal actin transport

Abstract

Recent advances in live cell imaging of F-actin structures, combined with pulse-chase imaging and computational modeling have suggested that actin is transported along the axon via biased polymerization of metastable actin fibers (actin trails). This mechanism is distinct from motor driven polymer transport, such as for neurofilaments and can be best described as molecular hitchhiking, where G-actin molecules are intermittently incorporated into actin fibers which grow preferentially in the anterograde direction. In this paper, we discuss how various axonal and actin trail parameters like axon diameter, trail nucleation rates, basal G-actin concentration, and trail length influence the transport rate. These predictions can help guide future experiments to verify this novel protein transport mechanism. We introduce a simplified, analytically solvable model of actin transport which relates these parameters to experimentally measurable quantities. We also discuss why a simple diffusion-based transport mechanism cannot explain bulk actin transport in the axon.