Single-protein Afm-based Force Spectroscopy Nyu-csmr

The recently developed single molecule force spectroscopy enables the detailed study of the mechanisms of protein unfolding and refolding under a stretching force. It has revealed many signatures of complexity of the underlying energy landscape that were previously overlooked in bulk experiments. For example, the broad distribution of unfolding times of the protein ubiquitin has been suggestive of glassy protein dynamics. During this twelve-week internship, I set out to test whether this complexity is related to structural features. Using a mutant protein, one can restrict the portion of the molecule exposed to force, thus diminishing its structural complexity. In this study, we found that indeed, reducing the structure to a single β-sheet gives rise to single exponential kinetics, characteristic of a two-state process. This has important consequences on how the architecture of the protein affects its mechanical properties.