Single-Molecule Mechanoenzymatics

The ability of cellular signaling networks to sense, process, and respond to internal and external stimuli relies on their specific detection and transduction based on molecular recognition. The molecular mechanisms by which force is specifically sensed by mechanoenzymatic processes, translated into biochemical signals, and wired to cellular signaling networks recently became accessible with single-molecule force spectroscopy. By stretching such mechanobiochemical converters along their natural reaction coordinate, complex mechanical activation pathways and subsequent biochemical reactions may be measured in a dynamic and highly precise manner. The discovered mechanisms have in common well-tuned force-induced conformational changes that lead to exposure of active recognition sites. Newly developed strategies allow investigators to test different conformational states for activity and to elucidate mechanical architectures leading to highly specific mechanical activation pathways. Here, we discuss the advances in the new field of single-molecule mechanoenzymatics and highlight complementary examples studied in bulk and in vivo.