Influence of membrane physical properties on binding kinetics of adhesion proteins

Cell–cell adhesion is mediated by the specific binding of membrane-anchored proteins and is essential for many biological processes, including tissue formation, immune responses, and cell signaling. How membrane mechanics affect the binding is still not well understood. Here, we use kinetic Monte Carlo simulations of a mesoscopic model to investigate how membrane roughness, bending rigidity, and the relative time scales of protein diffusion and membrane undulations affect binding kinetics of membrane-anchored proteins. We find that the two-dimensional binding constant K2D decreases with increasing membrane roughness ξ⊥ according to the expected roughness-dependent scaling relation. The off-rate constant koff is only weakly affected by membrane roughness, although fast membrane undulations and smaller bending rigidity κ can moderately enhance the off-rate. In contrast, the on-rate constant kon decreases strongly with increasing ξ⊥ and is further regulated by membrane bending rigidity and the timescale of membrane undulations. Our study provides a quantitative framework for understanding how membrane fluctuations regulate adhesion kinetics and offers physical insight relevant to the interpretation of cell adhesion experiments and the design of tunable membrane interfaces.