G0210202 Mechanical Behaviors of Neuro-filament:A Coarse Graining Simulation Study

Abstract

Neurofilaments (NFs) are a major constituent of nerve cell axons where they form a spacious network that aids in axonal transport and provides a structural scaffold within the long projections. NFs assemble from three subunit proteins of low (NFL), medium (NFM), and high (NFH) molecular weight into a semi flexible rod with radiating sidearms to form a bottlebrush-like structure. The sidearms of NFs have been proposed to be highly disordered, leading to entropically and electrostatically based interactions that play a key role in mediating interfilament spacing. Here, to investigate the mechanical behaviors of two interacting neurofilament sidearms, we performed molecular dynamics simulations using one bead represented one amino acid coarse graining model. We then measured the electrostatic interactions between the sidearms based on Debye-Huckel model. As a result, the repulsive interactions based on negative charges generate between NFLs, indicating that they form large interfilament spacing. On the other hand, the attractive interactions generate between NFMs. In comparison with recent experiments investigating condensed and expanded gel states, our results demonstrated that the local interactions between NF sidearms could regulate the network structure of NFs.