Conformational dynamics of neurofilament side-arms

The side-arms of neurofilaments (NFs) have been proposed to be highly disordered, leading to entropic repulsion that modulates interfilament spacing. To gain further insight into the dynamics and organization of the side-arms, we performed molecular dynamics simulations of neurofilament brushes using a coarse-grained model. The density profiles for three NF proteins, NF-L, NF-M, and phosphorylated NF-H (NF-HP), grafted to planar surfaces were calculated and examined as a function of component (salt, residues) and as a function of charge. Analysis of these profiles reveals that the NF with the shortest side arm, NF-L, is disproportionately long compared to the other NFs. The reason for difference is that NF-L is effectively a strong polyelectrolyte, while NF-M and NF-HP are effectively weaker polyelectrolytes. Further, we find cross-correlations between neurofilament side-arms within the brush, even for the NF-L polymers. These correlations occur because of strong attractions between the long sequence repeats of negative residues and the long postive residue repeats and impart a time average structure of the neurofilament brush that deviates from an ideal polymer in a theta solvent.