Geometric Signatures of Switching Behavior in Mechanobiology

The proteins involved in cells' mechanobiological processes have evolved specialized and surprising responses to applied forces. Biochemical transformations that show catch-to-slip switching and force-induced pathway switching serve important functions in cell adhesion, mechano-sensing and signaling, and protein folding. We show that these switching behaviors are generated by singularities in the flow field that describes force-induced deformation of bound and transition states. These singularities allow for a complete characterization of switching mechanisms in 2-dimensional (2D) free energy landscapes, and provide a path toward elucidating novel forms of switching in higher dimensional models. Remarkably, the singularity that generates a catch-slip switch occurs in almost every 2D free energy landscape, implying that almost any bond admitting a 2D model will exhibit catch-slip behavior under appropriate force. We apply our analysis to models of P-selectin and antigen extraction to illustrate how these singularities provide an intuitive framework for explaining known behaviors and predicting new behaviors.