Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: insights from computational model systems and theory

TL;DR

This paper reviews how membrane properties and protein anchoring influence the binding equilibrium and kinetics of membrane-anchored receptors and ligands, combining simulations and theory for new insights.

Contribution

It introduces a theoretical framework linking 2D membrane binding constants with 3D soluble receptor-ligand binding, supported by simulation results.

Findings

Membrane roughness significantly affects binding constants and rates.

A general relation between 2D and 3D binding constants is established.

Simulations confirm the impact of membrane fluctuations on binding kinetics.

Abstract

The adhesion of cell membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. In this article, we review recent results from simulations and theory that lead to novel insights on how the binding equilibrium and kinetics of these proteins is affected by the membranes and by the membrane anchoring and molecular properties of the proteins. Simulations and theory both indicate that the binding equilibrium constant K2D and the on- and off-rate constants of anchored receptors and ligands in their 'two-dimensional' (2D) membrane environment strongly depend on the membrane roughness from thermally excited shape fluctuations on nanoscales. Recent theory corroborated by simulations provides a general relation between K2D} and the binding constant K3D of soluble variants of the receptors and ligands that lack the membrane anchors and are free to diffuse in three dimensions (3D).