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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Chemistry and Physics of Lipids; v. 232, OCT 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/50983-3 - INCT 2014: fluidos complexos
• Beneficiário: Antonio Martins Figueiredo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/19077-1 - Desenvolvimento de novos adjuvantes de vacinas capazes de ativar células T CD1d-restritas
• Beneficiário: Julio Henrique Kravcuks Rozenfeld
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/13368-4 - Sistemas nanoestruturados: de modelos biomiméticos de membranas a carreadores de bioativos
• Beneficiário: Karin Do Amaral Riske
• Modalidade de apoio: Auxílio à Pesquisa - Temático