Geometric and thermodynamic restrictions for the self-assembly of glycosphingolipid-phospholipid systems.

The thermodynamic and geometrical features of possible self-assembled structures of a series of chemically related glycosphingolipids differing in the complexity of their polar headgroup, and of their mixture with phospholipids, have been predicted according to the theory of self-assembly of hydrocarbon amphiphiles of Israelachvili et al. ((1980) Q. Rev. Biophys. 13, 340-357). The type and number of carbohydrate residues in the oligosaccharide chain of the polar headgroup are of paramount importance to determine the characteristics and thermodynamic stability of the possible self-assembled structure. In single component systems, the general prediction of the theory is that smaller aggregates may form as the polar headgroup of the glycosphingolipid is more complex and as the lateral surface pressure is smaller. In noninteracting two-component glycosphingolipid-phospholipid systems, the thermodynamic stability and the overall geometry of the possible aggregate appear to be determined by the proportion and type of glycosphingolipid present. Large and abrupt changes of the possible free energy per molecule, radius of curvature, and predicted asymmetry ratio for a particular glycosphingolipid may be triggered by relatively small changes of the molecular parameters, lipid composition, lateral surface pressure or vice-versa. If intermolecular interactions are taken into account with respect to the predictions for an ideal, noninteracting system, the theory indicates that two-component bilayer vesicles of polysialoganglioside-phosphatidylcholine may be thermodynamically and geometrically more stable. On the other hand, for systems constituted by phosphatidylcholine and neutral glycosphingolipids or monosialogangliosides, the possible bilayer vesicle is predicted to be less stable than in the ideal, noninteracting case. The results emphasize the general validity of the theory as applied to glycosphingolipid-containing systems.