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

Author(s)

Martins, Leticia S. ^[1] ; Duarte, Evandro L. ^[2] ; Lamy, M. Teresa ^[2] ; Rozenfeld, Julio H. K. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biofis, Escola Paulista Med, R Botucatu 862, BR-04023062 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis, Rua Matao 1371, BR-05508090 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Chemistry and Physics of Lipids; v. 232, OCT 2020.
• Web of Science Citations: 0

Abstract

upsilon alpha-galactosylceramide (alpha-GalCer; KRN7000) strongly stimulates NKT cells. The structures of alpha-GalCer assemblies and of cationic DODAB bilayers containing alpha-GalCer were investigated by differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy. Assemblies of alpha-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% alpha-GalCer is miscible with the cationic lipid. ESR spectra show that alpha-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, alpha-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 alpha-GalCer to its long and saturated acyl chain. Possibly, alpha-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 C24:1 beta-glucosylceramide. Since the structure of delivery systems is critical to the biological activity of alpha-GalCer, this work certainly contributes to the planning and development of novel immunotherapeutic tools. (AU)

• FAPESP's process: 14/50983-3 - INCT 2014: complex fluids
• Grantee: Antonio Martins Figueiredo Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/19077-1 - Development of novel vaccine adjuvants capable of activating CD1d-restricted T cells
• Grantee: Julio Henrique Kravcuks Rozenfeld
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/13368-4 - Nanostructured systems: from membrane biomimetic models to carriers of bioactives
• Grantee: Karin Do Amaral Riske
• Support Opportunities: Research Projects - Thematic Grants