Stochastic models of polymerization based axonal actin transport

Abstract

Pulse-chase and radio-labeling studies have shown that actin is transported in bulk along the axon at rates consistent with slow axonal transport. In a recent paper, using a combination of live cell imaging, super resolution microscopy and computational modeling, we proposed that biased polymerization of metastable actin fibers (actin trails) along the axon shaft forms the molecular basis of bulk actin transport. The proposed mechanism is unusual, and can be best described as molecular hitch hiking, where G-actin molecules are intermittently incorporated into actin fibers which grow preferably in anterograde direction giving rise to directed transport, released after the fibers collapse only to be incorporated into another fiber. In this paper, we use our computational model to make additional predictions that can be tested experimentally to further scrutinize our proposed mechanism for bulk actin transport. In the previous paper the caliber of our model axon, the density of the actin nucleation sites to form the metastable actin fibers, the length distribution of the actin trails and their growth rate were adapted to the biologic axons used for measurements. Here we predict how the transport rate will change with axon caliber, density of nucleation sites, nucleation rates and trail lengths. We also discuss why a simple diffusion-based transport mechanism can not explain bulk actin transport.