A generic self-stabilization mechanism for biomolecular adhesions under load

TL;DR

This paper proposes a universal molecular mechanism inspired by cellular adhesions that enables biological systems to strengthen and stabilize their adhesions under load without active feedback, enhancing tissue integrity.

Contribution

It introduces a novel self-stabilization mechanism based on conformational changes of adhesion molecules, applicable to various biological adhesion networks, demonstrated in cellular systems.

Findings

Self-stabilization increases adhesion lifetimes across parameter ranges.

The mechanism operates without decreasing bond dissociation rates with force.

It naturally occurs in cellular adhesions involving talin and vinculin.

Abstract

Mechanical loading generally weakens adhesive structures and eventually leads to their rupture. However, biological systems can adapt to loads by strengthening adhesions, which is essential for maintaining the integrity of tissue and whole organisms. Inspired by cellular focal adhesions, we suggest here a generic, molecular mechanism that allows adhesion systems to harness applied loads for self-stabilization under non-equilibrium conditions -- without any active feedback involved. The mechanism is based on conformation changes of adhesion molecules that are dynamically exchanged with a reservoir. Tangential loading drives the occupation of some stretched conformation states out of equilibrium, which, for thermodynamic reasons, leads to association of further molecules with the adhesion cluster. Self-stabilization robustly increases adhesion lifetimes in broad parameter ranges. Unlike for catch-bonds, bond dissociation rates do not decrease with force. The self-stabilization principle can be realized in many ways in complex adhesion-state networks; we show how it naturally occurs in cellular adhesions involving the adaptor proteins talin and vinculin.