Influence of Brain Gangliosides on the Formation and Properties of Supported Lipid Bilayers

Abstract

This is a comprehensive study of the effects of the four major brain gangliosides (GM1, GD1b, GD1a, and GT1b) on the adsorption and rupture of phospholipid vesicles on SiO2 surfaces for the formation of supported lipid bilayer (SLB) membranes. Using quartz crystal microbalance with dissipation monitoring (QCM-D) we show that gangliosides GD1a and GT1b significantly slow the SLB formation process, whereas GM1 and GD1b have smaller effects. This is likely due to the net ganglioside charge as well as the positions of acidic sugar groups on ganglioside glycan head groups. Data is included that shows calcium can accelerate the formation of ganglioside-rich SLBs. Using fluorescence recovery after photobleaching (FRAP) we also show that the presence of gangliosides significantly reduces lipid diffusion coefficients in SLBs in a concentration-dependent manner. Finally, using QCM-D and GD1a-rich SLB membranes we measure the binding kinetics of an anti-GD1a antibody that has similarities to a monoclonal antibody that is a hallmark of a variant of Guillain-Barre syndrome.

Organization of gangliosides into membrane nanodomains

“…For example, Weng et al [226] have observed a decrease in the diffusion coefficient of Texas Red-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (TR-DHPE) of 9% and 16% in egg PC SLBs containing 2% and 5% of GM 1 , respectively, while Sagle et al have noted a 24% reduction in the diffusion coefficient of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3phosphoethanolamine (NBD-PE) when increasing the GM 1 concentration from 0 to 8% in a POPC SLBs [227]. Jordan et al [228] have also used FRAP to characterize the diffusion of TR-DHPE in DOPC SLBs containing 1 to 5% of GM 1 , GD 1 a, GD 1 b and GT 1 b, in the absence and presence of Ca 2+ . They have found that the increase in ganglioside concentration hinders diffusion of the probe with the effect being more pronounced for the larger GT 1 b. Interestingly, these studies justify their results by the presence of ganglioside clusters or nanodomains, but these have not been further characterized.…”