Bioengineering Lecture

Single-molecule manipulation studies open a door for a close-up investigation of complex biological interactions and properties at the molecular level. In these studies, single biomolecules are pulled while their force response is being monitored. The process is often nonequilibrium and therefore, interpretation of the results has been challenging. We used an atomic force microscope to pull proteins and DNA, and reconstructed the equilibrium free energy landscapes of the molecules using the recently derived nonequilibrium work theorem. In addition, the force response provides us a tool to examine the dynamics of biomolecular systems such as multimeric proteins and DNA. Applications of the technique in problems such as DNA overstretching transitions and mechanical activation of a key protein in blood coagulation, von Willebrand Factor, will also be presented.