Colloidal Stabilization of Neurofilaments and Microtubules
Abstract
The research supported by this award was based on the hypothesis that the interfilament distances between microtubules and neurofilaments are maintained by a polymer brush based mechanism, that results in what has been called colloidal stabilization. We suggest that failure of such stabilization may be related to neuropathologies such as ALS and Alzheimer's disease. To address this problem we used a set of biophysical methods, including atomic force microscopy, to investigate interfilament potentials. There are several main conclusions from the work under this award. First, microtubule associated proteins behave as though they are largely unstructured and can give rise to a long range repulsive force that is predominantly entropic in origin. This is an important finding that provides a biophysical mechanism that explains how microtubule spacing is maintained. Second, treating the unstructured proteins domains as polyelectrolytes shows how interfilament potentials between neurofilaments or micromicrotubules can be smoothly modulated by phosphorylation. Finally, the analysis of neurofilament distributions in axons shows that these can be recapitulated with a soft long range repulsion of the type generated by unstructured polymers. These findings support the main hypothesis and suggest a new way to think about axonal cytoskeleton and mechanisms of protein aggregation in neurodegeneration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA417089
Entities
People
- Jan H. Hoh
Organizations
- Johns Hopkins University