Abstract
Submicron scale domains of membrane-anchored receptors play an important role in cell signaling. Central questions concern the stability of these microdomains, and the mechanisms leading to the domain formation. In immune-cell adhesion zones, microdomains of short receptor-ligand complexes form next to domains of significantly longer receptor-ligand complexes. The length mismatch between the receptor-ligand complexes leads to membrane deformations and has been suggested as a possible cause of the domain formation. The domain formation is a nucleation and growth process that depends on the line tension and free energy of the domains. Using a combination of analytical calculations and Monte Carlo simulations, we derive here general expressions for the line tension between domains of long and short receptor-ligand complexes and for the adhesion free energy of the domains. We argue that the length mismatch of receptor-ligand complexes alone is sufficient to drive the domain formation, and obtain submicron-scale minimum sizes for stable domains that are consistent with the domain sizes observed during immune-cell adhesion.
Highlights
In the past years, microdomains of proteins in cell membranes have emerged as a central aspect of cell signaling [1,2,3,4]
We have found that large, repulsive glycoproteins and additional complexes with a length close to the T cell receptors (TCRs)-MHCpeptide complex, such as the CD2–CD48 complex [25], increase the tendency for domain formation [26]
Adhesion free energy of receptor-ligand domains The free energy of domains of long or short receptor-ligand complexes can be determined from the effective double-well adhesion potential of the membranes
Summary
Microdomains of proteins in cell membranes have emerged as a central aspect of cell signaling [1,2,3,4]. Several mechanisms have been proposed for the formation of TCR-MHCpeptide domains during T-cell adhesion These mechanisms are based on the actin cytoskeleton [10,11], enhanced cis-interactions between TCRs due to conformational changes after binding [1], pre-clustering of TCRs prior to adhesion [12,13], and the length difference between the TCR-MHCpeptide complexes and other receptor-ligand complexes and proteins in the T-cell adhesion zone [14,15,16,17,18,19,20,21,22]. Beyond certain threshold or critical concentrations of the receptors and ligands, the membrane-mediated repulsion leads to a segregation of TCR-MHCpeptide and integrin complexes into domains enriched in these complexes
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