Characterization of Symmetric and Asymmetric Lipid Bilayers Composed of Varying Concentrations of Ganglioside GM1 and DPPC

Gangliosides are a group of structurally diverse, sialic acid containing glycosphingolipids embedded into the membrane via their hydrophobic ceramide moiety. To gain atomic level insights into the structural perturbations caused by Galβ3GalNAcβ4(NeuAcα3)Galβ4Glc1Cer (GM1), molecular dynamics (MD) simulations of a 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayer containing GM1 at five different concentrations have been performed. Biological membranes contain GM1 only on the exoplasmic leaflet. However, vesicles prepared in the laboratory contain GM1 in both the leaflets albeit unequally. Hence, simulations were performed with GM1 present in only one (asymmetric bilayers) or in both of the leaflets (symmetric bilayers) of the bilayer. In symmetric bilayers, there is a decrease in surface area, an increase in deuterium order parameter, and an increase in peak-to-peak distance of DPPC with increasing concentration of GM1. Thus, the overall area of the lipid bilayer decreases (condensation effect) and the thickness increases with increasing concentrations of GM1. Even in asymmetric systems, decrease in surface area and increase in deuterium order parameter of hydrocarbon chains of DPPC are observed. However, the decrease in bilayer area and the increase in bilayer thickness are not as much as in the symmetric bilayer.