COLL 16 |
| Sanjay Kumar1, Rajendrani Mukhopadhyay1, Michael E. Paulaitis2, and Jan H. Hoh1. (1) Department of Physiology, Johns Hopkins University School of Medicine, 206 WBSB, 725 N. Wolfe St., Baltimore, MD 21205, (2) Department of Chemical Engineering, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218 |
| Axons require a structured cytoskeleton to maintain shape, resist mechanical stress, and transport intracellular cargo. Here we describe our efforts to probe interactions that organize neurofilaments (NFs), the most abundant cytoskeletal element in large, myelinated neurons. We have approached NF-NF interactions with multiple tools, including statistical mechanical analysis of intracellular NF distributions, recapitulation of NF distributions through Monte Carlo simulations, atomic force microscopy (AFM) imaging of isolated NFs and characterization of NF gels. Together, our studies support a model in which NFs interact in a phosphorylation-dependent manner through mutual steric repulsion mediated by their unstructured, C-terminal sidearm domains. Parallel AFM force measurements on microtubule-associated proteins provide evidence that a similar mechanism contributes to the maintenance of spacing between microtubules. Steric repulsion mediated by unstructured polypeptide domains is emerging as a central element in other biomacromolecular systems and suggests an interesting new direction for the design of protein-based biomaterials. |
|
Nanoscale Imaging of Biological Systems
Division of Colloid and Surface Chemistry |