Condensation of membrane receptors can be controlled via specific adhesion to supported lipid bilayers with nanoscale topography

Abstract

Developing physical methods to modulate biomolecular clusters and condensates on cell membranes is of great importance for understanding physiological and pathological processes as well as for stimulating novel therapeutic strategies. Here, we propose an effective means to control biomolecular condensation on the cell membrane via specific adhesion to a supported lipid bilayer (SLB) with nanoscale topography. The specific adhesion is mediated by receptors in the cell membrane that bind their ligands anchored in the SLB. Using Monte Carlo simulations and mean-field theory, we demonstrate that the nanoscale topography of the SLB can enhance condensation of the receptors associated with lipid microdomains. This enhancement originates from (i) an interplay between the receptor-ligand binding and membrane bending, (ii) an effective attraction between the receptor-ligand complexes induced by thermal undulations of the membrane, and (iii) a rigidity difference between the membrane matrix and lipid microdomains. Our results indicate that SLBs with nanoscale topography proves an effective physical stimulus for tuning condensation of membrane adhesion proteins and lipids in cell membranes, and can serve as a feasible option to control and direct cellular activities, e.g., stem cell differentiation for biomedical and therapeutic applications.