Plasticity of hydrogen bond networks regulates mechanochemistry of cell adhesion complexes

TL;DR

This paper presents a microscopic theory explaining how hydrogen bond network remodeling under force leads to catch-bonds in cell adhesion proteins, revealing a universal mechanism for force-regulated cellular interactions.

Contribution

The study introduces a quantitative model linking hydrogen bond network dynamics to catch-bond behavior, providing new insights into mechanochemistry of cell adhesion complexes.

Findings

Hydrogen bond network remodeling explains catch-bond formation.

Force-induced allosteric transitions maximize hydrogen bonds based on receptor structure.

Predicted effects of a specific ligand mutation on catch-bond behavior.

Abstract

Mechanical forces acting on cell adhesion receptor proteins regulate a range of cellular functions by formation and rupture of non-covalent interactions with ligands. Typically, force decreases the lifetimes of intact complexes (slip-bonds), making the discovery that these lifetimes can also be prolonged ("catch-bonds"), a surprise. We created a microscopic analytic theory by incorporating the structures of selectin and integrin receptors into a conceptual framework based on the theory of stochastic equations, which quantitatively explains a wide range of experimental data (including catch-bonds at low forces and slip-bonds at high forces). Catch-bonds arise due to force-induced remodeling of hydrogen bond networks, a finding that also accounts for unbinding in structurally unrelated integrin-fibronectin and actomyosin complexes. For the selectin family, remodeling of hydrogen bond networks drives an allosteric transition resulting in the formation of maximum number of hydrogen bonds determined only by the structure of the receptor and is independent of the ligand. A similar transition allows us to predict the increase in number of hydrogen bonds in a particular allosteric state of $\alpha_5 \beta_1$ integrin-fibronectin complex, a conformation which is yet to be crystallized. We also make a testable prediction that a single point mutation (Tyr51Phe) in the ligand associated with selectin should dramatically alter the nature of the catch-bond compared to the wild type. Our work suggests that nature utilizes a ductile network of hydrogen bonds to engineer function over a broad range of forces.