Differentiating R5l and wildtype tau using atomic force microscopy.

Abstract

Tau is a microtubule associated protein found in neuronal axons which regulates microtubule assembly and organization. Aberrant tau polymerization into neurofibrillary tangles is highly correlated with neurodegenerative diseases such as Alzheimer's disease. As a natively unstructured protein, it has eluded traditional protein structural characterization methods such as crystallography, but analysis with atomic force microscopy (AFM) offers a novel method to interrogate tau structure. When tau is adsorbed on the AFM tip and onto a flat mica surface, the N-terminal projection domains of the protein extend outwards to form polyelectrolyte brushes on both the tip and surface, allowing measurement of forces between the projection domains of the opposing layers of tau as the tip approaches the surface.