Lateral diffusion of receptor-ligand bonds in membrane adhesion zones: Effect of thermal membrane roughness

Abstract

Abstract. -The adhesion of cells is mediated by membrane receptors that bind to complementary ligands in apposing cell membranes. It is generally assumed that the lateral diffusion of mobile receptor-ligand bonds in membrane-membrane adhesion zones is slower than the diffusion of unbound receptors and ligands. We find that this slowing down is not only caused by the larger size of the bound receptor-ligand complexes, but also by thermal fluctuations of the membrane shape. We model two adhering membranes as elastic sheets pinned together by receptor-ligand bonds and study the diffusion of the bonds using Monte Carlo simulations. In our model, the fluctuations reduce the bond diffusion constant in planar membranes by a factor close to 2 in the biologically relevant regime of small bond concentrations.Introduction. -Advances in optical microscopy have made it possible to observe the diffusion of single lipid and protein molecules in biological membranes with a positional accuracy down to about 40 nm at ms time resolution [1,2]. Deviations from free Brownian motion were frequently found [2,3] and interpreted as the consequence of membrane microheterogeneity. Moreover, cis-interactions of mobile membrane proteins with cytoskeletal-anchored proteins or aggregates were identified via transient immobilization [4]. Trans-interactions between single cellular cadherin molecules and their soluble counterpart have been studied [5], paving the way for a characterization of membrane-membrane adhesion zones at the level of individual adhesion molecules.

Switching from Ultraweak to Strong Adhesion

“…[13][14][15][16][17][18][19]. The patch contains 64 binders placed on a 640 × 640 nm square lattice.…”

“…In addition, overall membrane roughness seems to be related to the density of bonds . [ 18 ] On a level of a single bond these effects are captured by an effective, density-dependent binding affi nity that is typically smaller than the intrinsic binding strength of the pair v 0 . [ 13 ] To fi nd the relation between the membrane roughness and the number of formed bonds, we constructed the analog of the experimental situation in silico and performed a set of Langevin simulations [ 13 − 19 ] of an adhered membrane segment of a size 0.6 μ m × 0.6 μ m, where we varied v 0 (e.g., the stability of bonds).…”

Random pinning limits the size of membrane adhesion domains

“…Consequently, understanding how adhesion domains form, and the factors that control their size, shape, and growth [3,4], is of profound practical importance. Extensive studies have been performed on theoretical models for singlebond dynamics [5], collective dynamics of discrete bonds [6][7][8][9][10], and employing effective potentials [11][12][13], as well as experimentally on cell-mimetic model systems [14,15] such as lipid bilayer vesicles with embedded ligands brought in the vicinity of receptors tethered to supported membranes [16][17][18][19][20].…”

Monte Carlo Investigation of Diffusion of Receptors and Ligands that Bind Across Opposing Surfaces

“…If the boundary were set far from center, to the outermost limit of the region where binding is possible in our current model, there would be no difference in results between the two binding models. Using a Metropolis scheme, as in Krobath et al .,18 where the probability of diffusion is proportional to the change in energy associated with the proposed diffusion hop, would result in behavior similar to our model, however, at a greater computational cost.…”

“…The shape of the interface, in turn, may strongly affect the motion of receptors that bind ligands on an opposing surface. For example, it has been shown that thermal roughness in membranes can reduce the diffusion coefficient of membrane-bound molecules by a factor of 2 18. Thus, in contrast to previous work, we study both cell–cell interfaces where the cell surfaces exhibit strong curvature, as is the case during the early stages of a cell–cell interaction (e.g., through protrusions10,13,36,38), and as a completely flat surfaces, as is the case during the late stages of cell–cell interaction 10,13,36,38.…”