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

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 receptor-ligand 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.Comment: Review article, 13 pages, 9 figures, to appear in Soft Matte

Dynamic phase separation of fluid membranes with rigid inclusions

Membrane shape fluctuations induce attractive interactions between rigid inclusions. Previous analytical studies showed that the fluctuation-induced pair interactions are rather small compared to thermal energies, but also that multi-body interactions cannot be neglected. In this article, it is shown numerically that shape fluctuations indeed lead to the dynamic separation of the membrane into phases with different inclusion concentrations. The tendency of lateral phase separation strongly increases with the inclusion size. Large inclusions aggregate at very small inclusion concentrations and for relatively small values of the inclusions' elastic modulus.Comment: 6 pages, 6 figure

Adhesion of Lipid Membranes Mediated by Electrostatic and Specific Interactions

AbstractWe used the micropipet aspiration technique for a study of biomembrane adhesion. Adhesion was caused by contact site A, a highly specific cell adhesion molecule, reconstituted in lipid vesicles of DOPC with 5 %(mol/mol) DOPE-PEG2000. We found adhesion and subsequent receptor aggregation in the contact zone. Additionally, electrostatic modulation of membrane adhesion was studied. Whereas addition of the negatively charged lipid SOPS to the lecithin (SOPC) host membrane suppressed adhesion due to electrostatic repulsion, a positively charged lipid (DOTAP) was surprisingly ineffective. This might be due to either phase separation of the mixture or DOTAP changing other membrane properties as bending stiffness and the Hamaker constant.</jats:p

Adhesion-Induced Receptor Segregation and Adhesion Plaque Formation: A Model Membrane Study

AbstractA model system to study the control of cell adhesion by receptor-mediated specific forces, universal interactions, and membrane elasticity is established. The plasma membrane is mimicked by reconstitution of homophilic receptor proteins into solid supported membranes and, together with lipopolymers, into giant vesicles with the polymers forming an artificial glycocalix. The homophilic cell adhesion molecule contact site A, a lipid-anchored glycoprotein from cells of the slime mold Dictyostelium discoideum, is used as receptor. The success of the reconstitution, the structure and the dynamics of the model membranes are studied by various techniques including film balance techniques, micro fluorescence, fluorescence recovery after photobleaching, electron microscopy, and phase contrast microscopy. The interaction of the functionalized giant vesicles with the supported bilayer is studied by reflection interference contrast microscopy, and the adhesion strength is evaluated quantitatively by a recently developed technique. At low receptor concentrations adhesion-induced receptor segregation in the membranes leads to decomposition of the contact zone between membranes into domains of strong (receptor-mediated) adhesion and regions of weak adhesion while continuous zones of strong adhesion form at high receptor densities. The adhesion strengths (measured in terms of the spreading pressure S) of the various states of adhesion are obtained locally by analysis of the vesicle contour near the contact line in terms of elastic boundary conditions of adhesion: the balance of tensions and moments. The spreading pressure of the weak adhesion zones is S≈10−9J/m2 and is determined by the interplay of gravitation and undulation forces whereas the spreading pressure of the tight adhesion domains is of the order S≈10−6J/m2

Specific biomembrane adhesion-Indirect lateral interactions between bound receptor molecules

We studied biomembrane adhesion using the micropipet aspiration technique. Adhesion was caused by contact site A, a laterally mobile and highly specific cell adhesion molecule from Dictyostelium discoideum, reconstituted in lipid vesicles of DOPC (L-alpha-dioleoylphosphatidylcholine) with an addition of 5 mol % DOPE-PEG(2000) (1,2-diacyl-sn-glycero-3-phosphatidylethanolamine-N-[poly(ethyleneglycol) 2000]). The "fuzzy" membrane mimics the cellular plasma membrane including the glycocalyx. We found adhesion and subsequent receptor migration into the contact zone. Using membrane tension jumps to probe the equation of state of the two-dimensional "gas" of bound receptor pairs within the contact zone, we found strong, attractive lateral interactions

Spreading of an anchorage-dependent cell on a selectively ligand-coated substrate mediated by receptor-ligand binding

10.1002/jbm.a.32258Journal of Biomedical Materials Research - Part A913806-81