Condensation and intracellular interaction of membrane-anchored receptors and ligands capable of forming catch and slip bonds

Gaining insights into the condensation and intracellular interaction of membrane-anchored receptors and ligands is critical for elucidating physiological and pathological mechanisms and for informing therapeutic development. The membrane-anchored receptors and ligands that can form catch or slip bond are often subjected to forces. A fundamental question remains of how the applied force affects the condensation and interaction of membrane-anchored receptors and ligands. By using a mesoscopic mechanical model, we have studied the response of catch- and slip-bond mediated adhesion system to tensile force. We find that the receptor-ligand binding affinity can be quantified by considering the effective receptor-ligand interaction energy, which takes into account the force regulation and the elastic response of receptor-ligand complexes. Further, our results reveal that, unlike the planar membrane system, the tensile force can facilitate protein condensation and phase separation for the adhesion system with flexible membranes in a bond-type and force-distribution dependent fashion. This force-induced protein condensation originates from the reduced energetic cost and the less conformational entropy loss of fluctuating membranes. Our findings indicate that the tensile force can serve as an effective physical stimulus for tuning condensation and interaction of membrane proteins, and provide potential guidance for drug design.