Principles Involved in Interpreting Single-Molecule Force Measurement of Biomolecules

Single-molecule manipulation techniques provide a unique tool for a close-up investigation of the complex biological properties and interactions. During the force measurement, a single molecule is pulled while its force response is monitored. However, quantifying these non-equilibrium data and using them to understand the structure-function relationship of biological systems have been challenging. We describe the mechanics of nanoscale biomolecules and the use of these force measurements for the free energy reconstruction using the recently derived non-equilibrium work theorem, i.e., Jarzynski’s equality. We also compare the results with those from other phenomenological approaches. Finally, mechanical characterization of systems such as overstretching transitions of DNA are presented, and the implications and challenges of these single-molecule force studies are discussed.