Biophys J, May 2002, p. 2360-2372, Vol. 82, No. 5

Relating Interactions between Neurofilaments to the Structure of Axonal Neurofilament Distributions through Polymer Brush Models

Sanjay Kumar,^* Xinghua Yin, Bruce D. Trapp, Jan H. Hoh,^* and Michael E. Paulaitis

 ^*Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205;  Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195; and  Department of Chemical Engineering, Johns Hopkins University, Baltimore, Maryland 21218 USA

Neurofilaments (NFs) have been proposed to interact with one another through mutual steric exclusion of their unstructured C-terminal "sidearm" domains, producing order in axonal NF distributions and conferring mechanical strength to the axon. Here we apply theory developed for polymer brushes to examine the relationship between the brush properties of the sidearms and NF organization in axons. We first measure NF-NF radial distribution functions and occupancy probability distributions for adult mice. Interpreting the probability distributions using information theory, we show that the NF distributions may be represented by a single pair potential of mean force. Then, to explore the relationship between model parameters and NF architecture, we conduct two-dimensional Monte Carlo simulations of NF cross-sectional distributions. We impose purely repulsive interaction potentials in which the sidearms are represented as neutral and polyelectrolyte chains. By treating the NFs as telechelic polymer brushes, we also incorporate cross-bridging interactions. Both repulsive potentials are capable of reproducing NF cross-sectional densities and their pair correlations. We find that NF structure is sensitive to changes in brush thickness mediated by chain charge, consistent with the experimental observation that sidearm phosphorylation regulates interfilament spacing. The presence of attractive cross-bridging interactions contributes only modestly to structure for moderate degrees of cross-bridging and leads to NF aggregation for extensive cross-bridging.

Biophys J, May 2002, p. 2360-2372, Vol. 82, No. 5
© 2002 by the Biophysical Society   0006-3495/02/05/2360/13  $2.00

This article has been cited by other articles:

				J. B. Jones and C. R. Safinya Interplay between Liquid Crystalline and Isotropic Gels in Self-Assembled Neurofilament Networks Biophys. J., July 15, 2008; 95(2): 823 - 835. [Abstract] [Full Text] [PDF]

				E. B. Zhulina and F. A. M. Leermakers A Self-Consistent Field Analysis of the Neurofilament Brush with Amino-Acid Resolution Biophys. J., September 1, 2007; 93(5): 1421 - 1430. [Abstract] [Full Text] [PDF]

				E. B. Zhulina and F. A. M. Leermakers Effect of the Ionic Strength and pH on the Equilibrium Structure of a Neurofilament Brush Biophys. J., September 1, 2007; 93(5): 1452 - 1463. [Abstract] [Full Text] [PDF]

				B. Windisch, D. Bray, and T. Duke Balls and Chains--A Mesoscopic Approach to Tethered Protein Domains Biophys. J., October 1, 2006; 91(7): 2383 - 2392. [Abstract] [Full Text] [PDF]

				O. I. Wagner, J. Ascano, M. Tokito, J.-F. Leterrier, P. A. Janmey, and E. L. F. Holzbaur The Interaction of Neurofilaments with the Microtubule Motor Cytoplasmic Dynein Mol. Biol. Cell, November 1, 2004; 15(11): 5092 - 5100. [Abstract] [Full Text] [PDF]