Protein Unfolding and Refolding Under Force: Methodologies for Nanomechanics

Abstract
An increasing number of inter‐ and intramolecular interactions can nowadays be probed using single‐molecule manipulation techniques. Protein unfolding and refolding is the most representative—though complex—of these interactions. Herein, we review the main modes of performing a force unfolding experiment: the velocity clamp and the new force clamp mode. We also compare some of the physical aspects behind the two most frequently used single‐molecule manipulation instrumentations: optical tweezers and atomic force microscopes.