Abstract
The adhesion zone of immune cells, the ‘immunological synapse’, exhibits characteristic domains of receptor–ligand complexes. The domain formation is probably 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, which bind to the T-cell receptor (TCR) and the receptor LFA1 in the cell membrane, the coexistence of domains of the 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 quite narrow ratio of ligand concentrations. In this paper, 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 us 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.
Highlights
In fluorescence experiments of T cells on supported membranes that contain mixtures of two of the three CD48 types, Milstein et al observed that CD2–CD48 wildtype complexes segregate from both CD2–CD48 variant complexes
For T cells adhering to supported membranes with MHCp and ICAM1, in contrast, domain coexistence has been observed for quite a wide range of MHCp and ICAM1 concentrations and affinities [8, 9, 15]
We have determined phase diagrams for cells adhering to supported membranes with anchored ligands
Summary
Cell adhesion involves length scales that differ by orders of magnitude (see figure 1). The two apposing membranes in the contact zone of cells or vesicles are divided into small patches [16]–[18], [20, 23], [29]–[36]. Each patch of the discrete membranes can only be occupied by one receptor or ligand molecule. Mobile receptor and ligand molecules diffuse by ‘hopping’ from patch to patch, and the thermal fluctuations of the membranes are reflected in variations of the local separation of apposing membrane patches. A receptor can bind to a ligand molecule if the ligand is located in the membrane patch apposing the receptor and if the local separation of the membranes is close to the length of the receptor–ligand complex (see figure 2 and below). In contrast, the distributions of receptor and ligand molecules on the membranes are described by continuous concentration profiles [38]–[48]
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