Date of Award


Degree Type


Degree Name

Doctor of Philosophy


The influence of naturally occurring glycosphingolipid (GSL) structural variations as modulators of glycolipid organization and dynamics was considered by wideline {dollar}\sp2{dollar}H-NMR in bilayer model membranes. Non-perturbing deuterium probes were placed at selected locations within polar and hydrophobic regions. A variety of environmental influences, which have been widely considered as major determinants of GSL function as recognition sites and structural elements, was examined.;GSL oligosaccharide orientation and motional order were monitored while systematically altering primary GSL structure changes and membrane environment. Each glycolipid, as a minor membrane component, demonstrated clear evidence of preferred average oligosaccharide orientation. Strikingly, the conformation and motional order of all the GSL headgroups monitored in fluid membranes were only modestly influenced by factors tested, including natural and artificially introduced variations to the GSL hydrophobic region, membrane fluidity, temperature, and presence of cholesterol or the NANA residue of gm{dollar}\sb1{dollar}. High Ca{dollar}\sp{lcub}2+{rcub}{dollar} concentrations produced spectral changes in asialo-gm{dollar}\sb1{dollar} (neutral GSL) and gm{dollar}\sb1{dollar} (charged), which may reflect generalized ion binding to the membrane.;Measurement of spectra from deuterons located in the hydrophobic region of the GSL revealed the effects of fatty acid variation. Results of GSL fatty acid hydroxylation (D- and L-isomers) overall suggested that one significant aspect of the {dollar}\alpha{dollar}-hydroxy group was to interfere with glycolipid packing amongst host phospholipids in the upper portion of the acyl chains. For the D-{dollar}\alpha{dollar}-hydroxy stereoisomer, there was some evidence of minor strengthening of interlipid interaction near the membrane surface. Effects of GSL unsaturation proved to be very similar to published data dealing with glycerol based lipids in cell and model membranes. Phase diagrams of N-stearoyl (C-18) and N-lignoceroyl (C-24) galactosylceramide in SOPC were produced. The fluidus curves of both systems were virtually superimposable while a major difference was seen in ordered phase behaviour. At low concentrations, the phase behaviour of the C-18 and C-24 GalCer systems were very similar in both fluid and gel phases. Unique behaviour was observed for the omega end of very long GSL fatty acids in fluid phospholipid membranes.



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