Date of Award
Doctor of Philosophy
While a receptor function for glycolipids and glycoproteins may be their ultimate role, such interactions cannot be fully understood without a knowledge of the behaviour of these molecules as isolated membrane components. As an example of a complex, neutral glycolipid, globoside was spin labelled on its terminal surgar residue and employed in model membranes to study headgroup dynamics. The labelled headgroup demonstrated a high degree of motional freedom which was only very modestly correlated with the fluidity of the membrane. In spite of the absence of charged sugar residues in globoside, the headgroup behaviour monitored here was similar to that of oligosaccharide chains on gangliosides and several sialic acid - rich glycoproteins.;Liposomes bearing ganglioside or glycophorin as receptor were exposed to the unmodified lectin, WGA, and examined by freeze-etch electron microscopy. The only identifiable lectin-induced change was lateral redistribution of receptor glycoproteins; ganglioside molecules showed some evidence of existing in small clusters but their distribution was apparently unaffected by lectin binding. In a DEPC/DPPC mixture, gangliosides GD(,1a) and GT(,1b) were found to disperse throughout the bilayer, though in small clusters, whereas GM(,1) had a tendency to phase separate into large patches.;The potential of membrane-bound macromolecules for shielding glycolipids from involvement in specific binding events was considered in model membranes. Serum albumin and dextran, conjugated to oleic acid, were used to generate bilayer membranes with a considerable layer of adsorbed peripheral material. Gangliosides dispersed in such membranes were subjected to attack by the enzyme, neuraminidase, in order to assess their accessibility. No significant reduction in ganglioside hydrolysis could be demonstrated. It was concluded that non-specific, physical shielding by macromolecules is an unlikely source of the often observed 'crypticity' of glycolipids at the cell surface.
Peters, Mark William, "Glycoconjugates In Model Membranes: Dynamics, Distribution And Interaction With Lectins" (1984). Digitized Theses. 1332.