Impact of receptor-ligand distance on adhesion cluster stability

TL;DR

This study models how receptor-ligand distance affects the stability of adhesion clusters, revealing bistability and stochastic destabilization at large separations through a master equation approach.

Contribution

It introduces a novel master equation incorporating cooperative binding via polymeric tethers, providing insights into adhesion cluster stability.

Findings

Bistability between bound and unbound states at intermediate distances.

Switching times between states are calculated.

Stochastic effects destabilize clusters at large separations.

Abstract

Cells in multicellular organisms adhere to the extracellular matrix through two-dimensional clusters spanning a size range from very few to thousands of adhesion bonds. For many common receptor-ligand systems, the ligands are tethered to a surface via polymeric spacers with finite binding range, thus adhesion cluster stability crucially depends on receptor-ligand distance. We introduce a one-step master equation which incorporates the effect of cooperative binding through a finite number of polymeric ligand tethers. We also derive Fokker-Planck and mean field equations as continuum limits of the master equation. Polymers are modeled either as harmonic springs or as worm-like chains. In both cases, we find bistability between bound and unbound states for intermediate values of receptor-ligand distance and calculate the corresponding switching times. For small cluster sizes, stochastic effects destabilize the clusters at large separation, as shown by a detailed analysis of the stochastic potential resulting from the Fokker-Planck equation.