A Single-Molecule Approach to Tau

Abstract

Tau is a protein associated with bundles of microtubules, while tau/tau interactions can lead to aggregates thought to underlie Alzheimer's disease. Here, we investigate the utility of a multiplexed single-molecule manipulation approach to give information on tau structure and tau/tau interactions: Previously we demonstrated the ability to perform several single molecule measurements in parallel in a multiplexed magnetic tweezers assay (Rev. Sci. Instrum. 79, 094301 (2008)), enhancing the statistical significance of the data. For testing the capability of this tool in protein folding studies, we present data on nucleic acid hairpins as a model system. We directly observe high resolution hairpin opening and closing events on several single molecule tethers simultaneously subject to the same critical force. We then describe experiments to observe the thermodynamics and kinetics of protein aggregation by i) immobilizing and studying tau in isolation then ii) studying interactions between immobilized tau with tau free in solution.