Slow Axonal Transport and Radial Diffusion of Neurofilaments

Neurofilaments (NFs) are the most abundant and space-filling structures in the neuronal axon and are cargo of slow axonal transport. They are transported along microtubule tracks and exhibit stop-and-go movement, i.e., long pauses interspersed with brief bursts of movement. We hypothesize that during long pauses, NFs detach from microtubules and radially diffuse in search for another microtubule track to continue their movement. In this study, we investigate the physics of radial diffusive search for randomly distributed microtubules across the axon to determine how the average binding rate depends on the density of microtubules, their sizes and the size of the NFs. We found that the binding rate of NFs is linearly proportional to the microtubule density for small densities, but unexpectedly transitions to a 3/2 power-law for a wide range of densities relevant for axonal transport. This 3/2 power law has profound physiological implications for the modulation of axon caliber during radial growth in development and the formation of axonal constriction of myelinated axons at the nodes of Ranvier.