Adhesion of membranes via receptor–ligand complexes: Domain formation, binding cooperativity, and active processes

Abstract

Cell membranes interact via anchored receptor and ligand molecules. Central questions on cell adhesion concern the binding affinity of these membrane-anchored molecules, the mechanisms leading to the receptorligand domains observed during adhesion, and the role of cytoskeletal and other active processes. In this review, these questions are addressed from a theoretical perspective. We focus on models in which the membranes are described as elastic sheets, and the receptors and ligands as anchored molecules. In these models, the thermal membrane roughness on the nanometer scale leads to a cooperative binding of anchored receptor and ligand molecules, since the receptor-ligand binding smoothens out the membranes and facilitates the formation of additional bonds. Patterns of receptor domains observed in Monte Carlo simulations point towards a joint role of spontaneous and active processes in cell adhesion. The interactions mediated by the receptors and ligand molecules can be characterized by effective membrane adhesion potentials that depend on the concentrations and binding energies of the molecules.

Model for Probing Membrane-Cortex Adhesion by Micropipette Aspiration and Fluctuation Spectroscopy

“…A different scaling is expected if the binding rate depends on the average position and fluctuations of the free membrane between anchoring points. If the on-rate obeys detailed balance, one expects r b,eq~r0 2 in the absence of a pressure difference (20,21). As discussed in the following sections, the results of micropipette experiments are consistent with a linear scaling s*~r 0 .…”

“…The adhesion of a flexible membrane on a substrate by means of discrete linkers has been extensively studied in the past (18)(19)(20)(21)(22)(23), mostly using computer simulations. It is a highly nontrivial problem due to the multiplicity of energy scales (membrane rigidity and tension, linker stiffness, and binding energy) and timescales (membrane and cytosol fluidity, linker's diffusion, and binding kinetics).…”

“…This assumption allows us to disregard membrane fluctuations between attachment points, and yields a simple analytical form for the unbinding transition. However, it does not capture binding cooperativity occurring due to the smoothing of membrane fluctuations near attachment points (19)(20)(21)(22)(23). Two relevant dimensionless quantities characterize the mechanics of the linkers: the kinetic ratio, c, and the ratio of the force on the membrane to an intrinsic force scale of the linkers, a, with ch k 0 off k on and ah sd r 0 k B T :…”

Spatial organization and signal transduction at intercellular junctions

“…In intercellular junctions, a protein-binding pair from opposite membranes can effectively prevent the interaction of a neighbouring proteinbinding pair if the intermembrane spacings of the pairs are very different 49 (FIG. 4b) or can induce clustering among similar proteins 50 . An important consequence of this is that intermembrane protein binding can exhibit cooperative effects between remote pairs of proteins that are not in direct contact.…”

Entropic attraction of adhesion bonds toward cell boundaries

“…Specific adhesion usually occurs in regions with high density of receptors and ligands. When facing a surface with enough ligands, the receptors may cluster into highly concentrated adhesion domains to establish strong binding [4,5]. Specific bioadhesion occurs in a variety of cellular processes, including binding of white blood cells to pathogens [6], binding and fusion of drug carrier liposome to target cells [7], cadherin-mediated adhesion of neighboring cells [8], focal adhesion of cells to the extracellular matrix [9], and cell signaling.…”