Segregation of receptor-ligand complexes in cell adhesion zones: Phase diagrams and role of thermal membrane roughness

Abstract

The adhesion zone of immune cells, the 'immunological synapse', exhibits characteristic domains of receptor-ligand complexes. The domain formation is likely caused by a length difference of the receptor-ligand complexes, and has been investigated in experiments in which T cells adhere to supported membranes with anchored ligands. For supported membranes with two types of anchored ligands, MHCp and ICAM1, that bind to the receptors TCR and LFA1 in the cell membrane, the coexistence of domains of TCR-MHCp and LFA1-ICAM1 complexes in the cell adhesion zone has been observed for a wide range of ligand concentrations and affinities. For supported membranes with long and short ligands that bind to the same cell receptor CD2, in contrast, domain coexistence has been observed for a rather narrow ratio of ligand concentrations. In this article, we determine detailed phase diagrams for cells adhering to supported membranes with a statistical-physical model of cell adhesion. We find a characteristic difference between the adhesion scenarios in which two types of ligands in a supported membrane bind (i) to the same cell receptor or (ii) to two different cell receptors, which helps to explain the experimental observations. Our phase diagrams fully include thermal shape fluctuations of the cell membranes on nanometer scales, which lead to a critical point for the domain formation and to a cooperative binding of the receptors and ligands.

23 pages, 6 figures

References in corpus (6)

• How cells tiptoe on adhesive surfaces before sticking
• Adhesion of membranes via receptor-ligand complexes: Domain formation, binding cooperativity, and active processes
• Binding cooperativity of membrane adhesion receptors
• Mechanisms of B cell Synapse Formation Predicted by Stochastic Simulation
• Fluctuation induced attraction between adhesion sites of supported membranes
• Membrane adhesion via competing receptor/ligand bonds

Cited by in corpus (6)

• Binding constants of membrane-anchored receptors and ligands: a general theory corroborated by Monte Carlo simulations
• Bending rigidities and interdomain forces in membranes with coexisting lipid domains
• Immune cells use active tugging forces to distinguish affinity and accelerate evolution
• First-passage time to clear the way for receptor-ligand binding in a crowded environment
• Effective free energy for pinned membranes
• Entropic attraction of adhesion bonds toward cell boundaries