Cis-interaction of ligands on a supported lipid bilayer affects their binding to cell adhesion receptors

Abstract

Cell adhesion on a supported lipid bilayer (SLB) functionalized with ligand proteins is a widely-used cell-mimetic model for the study of the trans receptor-ligand interaction that mediates the adhesion, and has been shown to play an important role in unravelling the molecular players in cell adhesion. Experimental studies of such cell-SLB adhesion systems often assume that there is no cis interactions between the ligands. An important question remains whether the cis-interaction affects the trans receptor-ligand interaction. Using a statistical-mechanical model and Monte Carlo simulations with biologically relevant parameters, we find that the attractive cis-interaction of strength 1 kBT between adjacent ligands on the SLB can lead to an amplification of both the affinity and cooperativity of the receptor-ligand binding, thereby facilitating the phase separation within the adhering cell membrane. In contrast, the adhesion system is less sensitive to the repulsive cis-interaction between adjacent ligands on the SLB. Our results suggest that the ligand-ligand cis-interaction should be carefully considered in the cell-SLB adhesion experiments.