Supramolecular organization of α-galactosylceramide in pure dispersions and in cationic DODAB bilayers

https://doi.org/10.1016/j.chemphyslip.2020.104963Get rights and content
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Highlights

  • α-GalCer decreases the gel-fluid transition temperature and cooperativity of DODAB bilayers.

  • α-GalCer decreases the packing of the gel phase but rigidifies the fluid phase of DODAB bilayers.

  • These effects could be explained by the amide bond connecting the sphingoid base to the acyl chain of α-GalCer.

Abstract

α-galactosylceramide (α-GalCer; KRN7000) strongly stimulates NKT cells. The structures of α-GalCer assemblies and of cationic DODAB bilayers containing α-GalCer were investigated by differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy. Assemblies of α-GalCer have a very tightly packed gel phase, causing spin labels to cluster and display spin exchange interactions. An endothermic phase transition is observed by DSC, leading to a fluid phase. This phase transition peak disappears upon mixing with DODAB, showing that up to 9 mol% α-GalCer is miscible with the cationic lipid. ESR spectra show that α-GalCer decreases DODAB gel phase packing, resulting in a decrease of gel-fluid transition temperature and cooperativity in DSC thermograms of mixed bilayers. In contrast, α-GalCer increases the rigidity of the fluid phase. These effects are probably due to the conformation of the rigid amide bond that connects the phytosphingosine base of α-GalCer to its long and saturated acyl chain. Possibly, α-GalCer adopts a V-shaped conformation because of the perpendicular orientation of the amide bond towards the axes of the hydrocarbon chains. Apparently, the effect of the amide bond configuration is a key structural feature for the interaction between ceramide-based glycolipids and DODAB molecules, since we have previously reported a similar decrease of gel phase packing and increase in fluid phase rigidity for DODAB bilayers containing C24:1β-glucosylceramide. Since the structure of delivery systems is critical to the biological activity of α-GalCer, this work certainly contributes to the planning and development of novel immunotherapeutic tools.

Keywords

α-galactosylceramide
glycosphingolipid
dioctadecyldimethylammonium bromide
cationic bilayers
differential scanning calorimetry
electron spin resonance spectroscopy

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