Number of Sialic Acid Residues in Ganglioside Headgroup Affects Interactions with Neighboring Lipids

Abstract

Monolayers of binary mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and asialo-(GA1), disialo-(GD1b) and trisialo-(GT1b) gangliosides were used to determine the effect of ganglioside headgroup charge and geometry on its interactions with the neighboring zwitterionic lipid. Surface pressure versus molecular area isotherm measurements along with concurrent fluorescence microscopy of the monolayers at the air-water interface were complemented with atomic force microscopy imaging of monolayers deposited on solid substrates. Results were used to further develop a proposed geometric packing model that the complementary geometry of DPPC and monosialoganglioside GM1 headgroups affects their close molecular packing, inducing condensation of the layer at small mol % of ganglioside. For GA1, GD1b, and GT1b, a similar condensing effect, followed by a fluidizing effect is seen that varies with glycosphingolipid concentration, but results do not directly follow from geometric arguments because less DPPC is needed to condense ganglioside molecules with larger cross-sectional areas. The variations in critical packing mole ratios can be explained by global effects of headgroup charge and resultant dipole moments within the monolayer. Atomic force microscopy micrographs further support the model of ganglioside-induced DPPC condensation with condensed domains composed of a striped phase of condensed DPPC and DPPC/ganglioside geometrically packed complexes at low concentrations.

Cholesterol enhances influenza binding avidity by controlling nanoscale receptor clustering

“…In analyzing the simulations, we defined GD1a multimers as two or more GD1a molecules separated by fewer than 8 Å, chosen as the distance to the first major peak in the radial distribution function of simulated lipids. These transient GD1a clusters are highly consistent with previous experimental thermodynamic data on ganglioside self-aggregation in lipid membranes 51 , 52 as well as data on transient G M1 nanoclusters. 53 , 54 In these simulations cholesterol was not more likely to be in contact with GD1a than other phospholipids, indicating a lack of preferential association.…”

“…We propose the following model for cholesterol enhancement of viral binding avidity ( Fig. 4A ): GD1a multimer formation is enthalpically favorable due to glycan–glycan interactions 52 but entropically disfavored due to steric confinement of lipid tails within multimers. Cholesterol lowers this entropic penalty of association by ordering lipid tails of a monomeric ganglioside and allows the enthalpy of multimerization to dominate the free energy of association.…”

Self-Assembly in Ganglioside‒Phospholipid Systems: The Co-Existence of Vesicles, Micelles, and Discs

“…The sialic acid residue of GM1 has a pKa of ca. 2.7 [35] and the ganglioside headgroup is therefore expected to carry one negatively charge for the present pH conditions as well as neutral conditions. The mildly acidic pH is relevant to some cellular environments, such as endosomes and lysosomes.…”

Monolayers of Carbohydrate-Containing Lipids at the Water- Air Interface

“…This effect has been credited to the complimentary geometrical structures of GM1 and DPPC, intermolecular hydrogen-bonding between the sugar groups and to alignment of the dipole moment of DPPC with the negative charge on the sialic acid residue. Recently, a study was conducted to understand the impact of gangliosides on the surrounding lipids and see if previous knowledge of the GM1/DPPC system can be used for generalization over a range of other gangliosides [78]. Three gangliosides with the same ceramide backbone but different numbers of sialic acid were investigated.…”