Which Moiety Drives Gangliosides to Form Nanodomains?

• DOI: 10.1021/acs.jpclett.3c00761
• Publication Date: 2023-06-16T19:44:10Z
• Authors: David Davidović; Mercedes Kukulka; Maria J. Sarmento; Ilya Mikhalyov; Natalia Gretskaya; Barbora Chmelová; Joana C. Ricardo; Martin Hof; Lukasz Cwiklik; Radek Šachl
• Keywords: Moiety; Ganglioside; Glycosphingolipid

Gangliosides are important glycosphingolipids involved in a multitude of physiological functions. From physicochemical standpoint, this is related to their ability self-organize into nanoscopic domains, even at molar concentrations one per 1000 lipid molecules. Despite recent experimental and theoretical efforts suggesting that hydrogen bonding network crucial for nanodomain stability, the specific ganglioside moiety decisive development these nanodomains has not yet been identified. Here, we combine an technique achieving nanometer resolution (Förster resonance energy transfer analyzed by Monte Carlo simulations) with atomistic molecular dynamic simulations demonstrate sialic acid (Sia) residue(s) oligosaccharide headgroup dominates between gangliosides, driving formation absence cholesterol or sphingomyelin. Consequently, clustering pattern asialoGM1, Sia-depleted glycosphingolipid bearing three glyco moieties, more similar structurally distant sphingomyelin than closely gangliosides GM1 GD1a two Sia groups, respectively.