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

TL;DR

This paper models the formation of receptor-ligand domains in immune cell adhesion zones, revealing how membrane fluctuations and ligand-receptor interactions influence domain coexistence and phase behavior.

Contribution

It introduces a detailed statistical-physical model that incorporates thermal membrane roughness to explain domain formation and coexistence in cell adhesion zones.

Findings

Identifies differences in domain formation when ligands bind to same or different receptors.

Provides phase diagrams predicting domain coexistence under various conditions.

Highlights the role of membrane fluctuations in critical behavior and cooperative binding.

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.