Geometric Signatures of Switching Behavior in Mechanobiology

The proteins involved in cell's mechanobiological processes have evolved specialized and surprising responses to applied forces. One example is catch-slip bonding, where a protein-protein bond switches from increasing strength to decreasing strength under increasing force. Another example is force-induced pathway switching, where a multi-pathway biochemical transformation switches from one pathway to another under applied force. These force-activated switching behaviors are important in various biological functions, from cell adhesion and mechanosensing, to molecular motors, proofreading, and antigen discrimination. We develop a theoretical framework that unifies these switching behaviors and identifies the signatures of a system's free energy landscape that generate specific switches. Remarkably, we find that almost every 2-dimensional bond will show catch-slip behavior under an appropriate pulling force—no specialized mechanisms are required. We use this framework to identify the signatures of switching in established catch bond models and we propose course-grained free energy landscapes for P-selectin, integrin, and actin/myosin catch bonds based on experimental data. Our framework suggests design principles for engineering novel bond behaviors and provides clues how sophisticated bonding mechanisms may have evolved from simple bonds.