High-Resolution Optical Tweezers for Single-Molecule Manipulation

Forces hold everything together and determine its structure and dynamics. In particular, tiny forces of 1-100 piconewtons govern the structures and dynamics of biomacromolecules. These forces enable folding, assembly, conformational fluctuations, or directional movements of biomacromolecules over sub-nanometer to micron distances. Optical tweezers have become a revolutionary tool to probe the forces, structures, and dynamics associated with biomacromolecules at a single-molecule level with unprecedented resolution. In this review, we introduce the basic principles of optical tweezers and their latest applications in studies of protein folding and molecular motors. We describe the folding dynamics of two strong coiled coil proteins, the GCN4-derived protein pIL and the SNARE complex. Both complexes show multiple folding intermediates and pathways. ATP-dependent chromatin remodeling complexes translocate DNA to remodel chromatin structures. The detailed DNA translocation properties of such molecular motors have recently been characterized by optical tweezers, which are reviewed here. Finally, several future developments and applications of optical tweezers are discussed. These past and future applications demonstrate the unique advantages of high-resolution optical tweezers in quantitatively characterizing complex multi-scale dynamics of biomacromolecules.