Binding kinetics of membrane-anchored receptors and ligands: molecular dynamics simulations and theory

Abstract

The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring of the proteins. In this article, we (i) present detailed data for the binding of membrane-anchored proteins from coarse-grained molecular dynamics simulations, and (ii) provide a theory that describes how the binding kinetics depends on the average separation and thermal roughness of the adhering membranes, and on the anchoring, lengths, and length variations of the proteins. An important element of our theory is the tilt of bound receptor-ligand complexes and transition-state complexes relative to the membrane normals. This tilt results from an interplay of the anchoring energy and rotational entropy of the complexes and facilitates the formation of receptor-ligand bonds at membrane separations smaller than the preferred separation for binding. In our simulations, we have considered both lipid-anchored and transmembrane receptor and ligand proteins. We find that the binding equilibrium constant and binding on-rate constant of lipid-anchored proteins are considerably smaller than the binding constant and on-rate constant of rigid transmembrane proteins with identical binding domains.

arXiv comment13 pages, 6 figures; to appear in J. Chem. Phys

References in corpus (5)

• Mechanisms of pattern formation during T cell adhesion
• Binding cooperativity of membrane adhesion receptors
• Binding constants of membrane-anchored receptors and ligands: a general theory corroborated by Monte Carlo simulations
• Binding kinetics of membrane-anchored receptors and ligands: molecular dynamics simulations and theory
• Coexistence of dilute and densely packed domains of ligand-receptor bonds in membrane adhesion

Cited by in corpus (4)

• Binding constants of membrane-anchored receptors and ligands: a general theory corroborated by Monte Carlo simulations
• Binding kinetics of membrane-anchored receptors and ligands: molecular dynamics simulations and theory
• Binding equilibrium and kinetics of membrane-anchored receptors and ligands in cell adhesion: insights from computational model systems and theory
• Criticality in Cell Adhesion