Molecular mechanisms determining the strength of receptor-mediated intermembrane adhesion

Abstract

The strength of receptor-mediated cell adhesion is directly controlled by the mechanism of cohesive failure between the cell surface and underlying substrate. Unbinding can occur either at the locus of the specific bond or within the bilayer, which results in tearing the hydrophobic anchors from the membrane interior. In this work, the surface force apparatus has been used to investigate the relationship between the receptor-ligand bond affinities and the dominant mechanism of receptor-coupled membrane detachment. The receptors and ligands used in this study were membrane-bound streptavidin and biotin analogs, respectively, with solution affinities ranging over 10 orders of magnitude. With the optical technique of the surface force apparatus, the occurrence of membrane rupture was directly visualized in situ. The latter observations together with measurements of the corresponding intermembrane adhesive strengths were used to identify the dominant failure pathway for each streptavidin-analog pair. Even in cases where the membrane pull-out energy exceeded the equilibrium bond energy, cohesive failure occurred within the membrane interior at nearly all bond affinities considered. These results are consistent with previous findings and provide direct support for the commonly held view that, under nonequilibrium conditions of applied external stress, the gradient of the bond energy, not the equilibrium bond energy alone, determines the adhesive strength. Furthermore, our findings directly demonstrate that, in the presence of competing failure mechanisms, the preferred detachment mechanism- hence, the adhesive strength-will be determined by the bond that exhibits the weakest tensile strength. Because the tensile strength is determined by the gradient of the unbinding energy, the critical detachment force will be determined by both the bond energy and the effective bond length.

Characterizing the interactions between GPI-anchored alkaline phosphatases and membrane domains by AFM

“…5). Such an effect is in accordance with the low forces required to extract phospholipids [30,58], the recovering protein anchored to the membrane via a myristic acid [24] and BIAP [21] from a bilayer. The extraction force required might also differ between fluid and ordered phases and, in our experience, could occur in both contact and oscillating modes.…”

Direct molecular force measurements of multiple adhesive interactions between cadherin ectodomains

“…We observed this behavior in five independent experiments with three separate protein preparations. The reproducibility both of the force curves and of the adhesion measured after initial detachment also showed that the lipid anchors did not pull out of the membrane (29). This indicates that rupture indeed occurred at the protein-protein contacts.…”

“…In all previous force measurements of protein-ligand interactions, bond failure results in the abrupt snap of the molecules out of adhesive contact (14,15,(25)(26)(27)(28)(29)(30)(31)(32). By contrast, the cadherin unbinding profile (Fig.…”

Fusion of reconstituted influenza virus envelopes with liposomes mediated by streptavidin/biotin interactions

“…Thus, streptavidin/biotin-mediated targeting of virosomes to liposomes specifically depended on simultaneous interaction of streptavidin with virosomal and liposomal biotin. The virosome and liposome membranes which fuse in this study are separated by the diameter of the streptavidin molecule, which is about 4.5 nm [16]. The interesting relationship between this distance and the extent of fusion may be investigated further by the use of lipophilic biotin ligands with spacers of different lengths.…”