Protein friction plays a fundamental role in regulating biomolecular interactions, yet it has remained largely inaccessible to direct experimental observation. We present a nanoscale approach using atomic force microscopy (AFM) in friction force mode (FFM) to visualize and quantify protein friction with subnanometer resolution. Functionalized AFM tips carrying -NH 2 and -COOH groups were used to mimic protein termini and probe bacteriorhodopsin (bR) in its native purple membrane. This enabled us to map frictional interactions, distinguish electrostatic from structural contributions, and identify specific binding sites on the protein surface. Analysis of velocity-dependent friction and force-distance measurements provided quantitative kinetic and thermodynamic parameters of bond rupture, consistent with the Prandtl-Tomlinson model. Our results establish FFM as a powerful method for directly probing protein friction and dynamics, offering mechanistic insight into processes, such as protein diffusion, transport, and mechanotransduction.
Mingdong Dong (Sun,) studied this question.