title: The effects of globotriaosylceramide tail saturation level on bilayer phases.
abstract: Globotriaosylceramide (Gb3) is a glycosphingolipid present in the plasma membrane that is the natural receptor of the bacterial Shiga toxin. The unsaturation level of Gb3 acyl chains has a drastic impact on lipid bilayer properties and phase behaviour, and on many Gb3-related cellular processes. For example: the Shiga toxin B subunit forms tubular invaginations in the presence of Gb3 with an unsaturated acyl chain (U-Gb3), while in the presence of Gb3 with a saturated acyl chain (S-Gb3) such invagination does not occur. We have used all-atom molecular dynamics simulations to investigate the effects of the Gb3 concentration and its acyl chain saturation on the phase behaviour of a mixed bilayer of dioleoylphosphatidylcholine and Gb3. The simulation results show that: (1) the Gb3 acyl chains (longer tails) from one leaflet interdigitate into the opposing leaflet and lead to significant bilayer rigidification and immobilisation of the lipid tails. S-Gb3 can form a highly ordered, relatively immobile phase which is resistant to bending while these changes for U-Gb3 are not significant. (2) At low concentrations of Gb3, U-Gb3 and S-Gb3 have a similar impact on the bilayer reminiscent of the effect of sphingomyelin lipids and (3) At higher Gb3 concentrations, U-Gb3 mixes better with dioleoylphosphatidylcholine than S-Gb3. Our simulations also provide the first molecular level structural model of Gb3 in membranes.
authors.affiliation: Center for Biomembrane Physics (MEMPHYS), Department of Physics, Chemistry and Pharmacy (FKF), University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. hkhandel@sdu.dk.
authors.forename: Weria
authors.initials: W
authors.lastname: Pezeshkian
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Chaban
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Julian
authors.initials: J
authors.lastname: Shillcock
authors.forename: John H
authors.initials: JH
authors.lastname: Ipsen
authors.forename: Himanshu
authors.initials: H
authors.lastname: Khandelia
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D014281:Trihexosylceramides / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D014281:Trihexosylceramides; C018549:globotriaosylceramide; C017251:1,2-oleoylphosphatidylcholine