Abstract
Gangliosides areimportant glycosphingolipids involvedin a multitudeof physiological functions. From a physicochemical standpoint, thisis related to their ability to self-organize into nanoscopic domains,even at molar concentrations of one per 1000 lipid molecules.
Despiterecent experimental and theoretical efforts suggesting that a hydrogenbonding network is crucial for nanodomain stability, the specificganglioside moiety decisive for the development of these nanodomainshas not yet been identified. Here, we combine an experimental techniqueachieving nanometer resolution (Fo''rster resonance energy transferanalyzed by Monte Carlo simulations) with atomistic molecular dynamicsimulations to demonstrate that the sialic acid (Sia) residue(s) atthe oligosaccharide headgroup dominates the hydrogen bonding networkbetween gangliosides, driving the formation of nanodomains even inthe absence of cholesterol or sphingomyelin.
Consequently, the clusteringpattern of asialoGM(1), a Sia-depleted glycosphingolipidbearing three glyco moieties, is more similar to that of structurallydistant sphingomyelin than that of the closely related gangliosides GM(1) and GD(1a) with one and two Sia groups, respectively.