Cell-cell adhesion mediated by mobile receptor-ligand pairs

Abstract

This thesis aims at a quantitative understanding of the physical processes in cell-cell adhesion caused by mobile cell adhesion molecules. To unequivocally separate physical processes from active biological cell response, a biomimetic model system was developed. It consisted of a giant unilamellar vesicle adhering via specific ligand-receptor interactions to a solid supported lipid bilayer. Adhesion was mediated by either biotin-neutravidin (an avidin analogue) or the extracellular domains of the homophilic cell adhesion molecule E-cadherin. A microscope was modified for simultaneous application of fluorescence microscopy and microinterferometry. <br /> In membrane adhesion mediated by both binding pairs in high concentration the final equilibrium was characterized with respect to membrane distance, tension, and adhesion energy density with the help of microinterferometry. Fluorescently labelled neutravidin was used to infer the receptor distribution and concentration beneath the adhering vesicle. Moreover, the fluidity of the SLB and the diffusion of the receptors was studied during vesicle adhesion by continuous photobleaching. Dynamics of vesicle adhesion (nucleation, growth and saturation) were analyzed for a broad range of receptor-ligand concentrations for strong binding and at high concentrations for weak binding.