Molecular Quakes and Neurofilament movement

Neurofilaments (NFs) are abundant protein polymers of the axonal cytoskeleton that determine axon caliber, which is important for neuronal function. The NFs are aligned in parallel along the long axis of the axon, spaced apart by a dense border of lateral sidearm projections that interact with neighboring NFs through weak electrostatic forces. NFs are also cargoes of axonal transport, propelled along microtubule tracks by molecular motors. These polymer cargos are assembled in the cell body and move along the axon in a stop-and-go manner, alternating between brief bursts of rapid movement interrupted by prolonged pauses. The mechanism for the intermittent nature of this movement is unknown. Here we show that this can be explained by the stochastic and reversible association of NF sidearms with neighboring NFs. When a driving force is applied to a pausing filament, tension builds along the length of the NF. As sidearm linkages break under this force, the force is born by successively fewer sidearms, resulting in an increased rate of detachment, abrupt release, and punctuated sudden NF movement. This resembles the movement of tectonic plates along fault lines, where tension buildup is released in punctuated events, the earthquakes. Just like earthquakes, molecular quakes are power-law distributed in amplitude. We demonstrate the model's viability by comparing the predicted behavior with high-resolution kymographic recordings of NF movement in axons.