Gangliosides containing different numbers of sialic acids affect the morphology and structural organization of isotropic phospholipid bicelles

Presence of sialic acid distinguishes gangliosides from other glycosphingolipids, helps maintain membrane structure and organization as well as acts as anchors for lectins, toxins and pathogens. The number and position of the sialic acid residues on gangliosides appear to influence the binding affinity and specificity of gangliosides. We have investigated the dependence of bicellar properties on sialic acids using monosialo1 (GM1), disialo1b (GD1b) and trisialo1a (GT1a) gangliosides incorporated in phospholipid bicelles. TEM, AFM and DLS show that increasing numbers of sialic acid moieties per ganglioside results in an increase in bicelle size. DPH fluorescence anisotropy results suggest that with incorporation of gangliosides in bicelles the orientational order of the hydrocarbon chains increases. Fluorescence anisotropy was used to explore the effect of gangliosides on lateral phase separation in ganglioside enriched bicelles. GM1 and GT1a exhibited a low Tm melting domain (DMPC rich) and a high Tm melting domain (ganglioside rich). For GD1b containing bicelles, no significant phase separation was observed, suggesting a single homogeneous phase. Symmetric and antisymmetric stretching vibrational bands of methylene shift to a lower wave number, implying acyl chain order decreasing as GT1a ≪ GM1 < GD1b. The results collectively indicate that increase in sialic acids on gangliosides exhibit no obvious trend but produce diversity in bicellar morphology and interactions at molecular level.

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► Bicelles containing gangliosides with different number of sialic acids are characterized.
► FT-IR spectra provides sialic acid signature of gangliosides in the bicelles.
► With increased number of sialic acid, size and bilayer thickness of the bicelles increase.
► Bicellar nature remains fast-tumbling and isotropic.