Protein unfolding and refolding under force: Methodologies for nanomechanics

An increasing number of inter- and intramoleculor 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 con also compare some of the physical aspects behind the two most frequently used single-molecule manipulation instrumentations: optical tweezers and atomic force microscopes.