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.