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含 C24:1 β-葡糖基神经酰胺的阳离子 DODAB 双层结构的特性分析。

Structural characterization of cationic DODAB bilayers containing C24:1 β-glucosylceramide.

机构信息

Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu 862, 04023-062 São Paulo, SP, Brazil.

Instituto de Física, Universidade de São Paulo, CP 66318, CEP 05315-970 São Paulo, SP, Brazil.

出版信息

Biochim Biophys Acta Biomembr. 2019 Mar 1;1861(3):643-650. doi: 10.1016/j.bbamem.2018.12.018. Epub 2019 Jan 3.

DOI:10.1016/j.bbamem.2018.12.018
PMID:30611744
Abstract

The effect of 5 mol%, 9 mol%, and 16 mol% of C24:1 β-glucosylceramide (βGlcCer) on the structure of cationic DODAB bilayers was investigated by means of differential scanning calorimetry (DSC), electron spin resonance (ESR) spectroscopy and fluorescence microscopy. βGlcCer is completely miscible with DODAB at all fractions tested, since no domains were observed in fluorescence microscopy or ESR spectra. The latter showed that βGlcCer destabilized the gel phase of DODAB bilayers by decreasing the gel phase packing. As a consequence, βGlcCer induced a decrease in the phase transition temperature and cooperativity of DODAB bilayers, as seen in DSC thermograms. ESR spectra also showed that βGlcCer induced an increase in DODAB fluid phase order and/or rigidity. Despite their different structures, a similar effect of loosening the gel phase packing and turning the fluid phase more rigid/organized has also been observed when low molar fractions of cholesterol were incorporated in DODAB bilayers. The structural characterization of mixed membranes made of cationic lipids and glucosylceramides may be important for developing novel immunotherapeutic tools such as vaccine adjuvants.

摘要

通过差示扫描量热法(DSC)、电子自旋共振(ESR)光谱和荧光显微镜研究了 5 mol%、9 mol%和 16 mol%的 C24:1 β-葡糖基神经酰胺(βGlcCer)对阳离子 DODAB 双层结构的影响。βGlcCer 在所有测试的分数中与 DODAB 完全混溶,因为在荧光显微镜或 ESR 光谱中没有观察到域。后者表明,βGlcCer 通过降低凝胶相的堆积来破坏 DODAB 双层的凝胶相。因此,正如 DSC 热谱图所示,βGlcCer 诱导 DODAB 双层的相变温度和协同性降低。ESR 光谱还表明,βGlcCer 诱导 DODAB 流体相有序性和/或刚性增加。尽管它们的结构不同,但当低摩尔分数的胆固醇掺入 DODAB 双层时,也观察到了类似的疏松凝胶相堆积和使流体相更刚性/有序的效果。研究由阳离子脂质和神经酰胺组成的混合膜的结构特征可能对于开发新型免疫治疗工具,如疫苗佐剂非常重要。

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