TY - JOUR

T1 - The effects of globotriaosylceramide tail saturation level on bilayer phases

AU - Pezeshkian, Weria

AU - Chaban, Vitaly V.

AU - Johannes, Ludger

AU - Shillcock, Julian

AU - Ipsena, John H.

AU - Khandelia, Himanshu

PY - 2015

Y1 - 2015

N2 - Globotriaosylceramide (Gb(3)) is a glycosphingolipid present in the plasma membrane that is the natural receptor of the bacterial Shiga toxin. The unsaturation level of Gb(3) acyl chains has a drastic impact on lipid bilayer properties and phase behaviour, and on many Gb(3)-related cellular processes. For example: the Shiga toxin B subunit forms tubular invaginations in the presence of Gb(3) with an unsaturated acyl chain (U-Gb(3)), while in the presence of Gb(3) with a saturated acyl chain (S-Gb(3)) such invagination does not occur. We have used all-atom molecular dynamics simulations to investigate the effects of the Gb(3) concentration and its acyl chain saturation on the phase behaviour of a mixed bilayer of dioleoylphosphatidylcholine and Gb(3). The simulation results show that: (1) the Gb(3) 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-Gb(3) can form a highly ordered, relatively immobile phase which is resistant to bending while these changes for U-Gb(3) are not significant. (2) At low concentrations of Gb(3), U-Gb(3) and S-Gb(3) have a similar impact on the bilayer reminiscent of the effect of sphingomyelin lipids and (3) At higher Gb(3) concentrations, U-Gb(3) mixes better with dioleoylphosphatidylcholine than S-Gb(3). Our simulations also provide the first molecular level structural model of Gb(3) in membranes.

AB - Globotriaosylceramide (Gb(3)) is a glycosphingolipid present in the plasma membrane that is the natural receptor of the bacterial Shiga toxin. The unsaturation level of Gb(3) acyl chains has a drastic impact on lipid bilayer properties and phase behaviour, and on many Gb(3)-related cellular processes. For example: the Shiga toxin B subunit forms tubular invaginations in the presence of Gb(3) with an unsaturated acyl chain (U-Gb(3)), while in the presence of Gb(3) with a saturated acyl chain (S-Gb(3)) such invagination does not occur. We have used all-atom molecular dynamics simulations to investigate the effects of the Gb(3) concentration and its acyl chain saturation on the phase behaviour of a mixed bilayer of dioleoylphosphatidylcholine and Gb(3). The simulation results show that: (1) the Gb(3) 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-Gb(3) can form a highly ordered, relatively immobile phase which is resistant to bending while these changes for U-Gb(3) are not significant. (2) At low concentrations of Gb(3), U-Gb(3) and S-Gb(3) have a similar impact on the bilayer reminiscent of the effect of sphingomyelin lipids and (3) At higher Gb(3) concentrations, U-Gb(3) mixes better with dioleoylphosphatidylcholine than S-Gb(3). Our simulations also provide the first molecular level structural model of Gb(3) in membranes.

KW - FORCE-FIELD

KW - MOLECULAR-DYNAMICS

KW - B-SUBUNIT

KW - MEMBRANE

KW - GROMACS

KW - RECEPTOR

KW - CHAIN

KW - SPHINGOMYELIN

KW - VALIDATION

KW - ANTIGEN

U2 - 10.1039/c4sm02456g

DO - 10.1039/c4sm02456g

M3 - Journal article

VL - 11

SP - 1352

EP - 1361

JO - Soft Matter

JF - Soft Matter

SN - 1744-683X

IS - 7

ER -