de Andrade Lucas, Duarte Evandro L, Lamy M Teresa, Rozenfeld Julio H K
Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, R. Botucatu 862, 04023-062São Paulo, São Paulo, Brazil.
Instituto de Física, Universidade de São Paulo, Rua do Matão 1371, 05508090São Paulo, São Paulo, Brazil.
ACS Omega. 2023 Feb 2;8(6):5306-5315. doi: 10.1021/acsomega.2c06189. eCollection 2023 Feb 14.
C24:1 sulfatide (SF) is an endogenous activator of type II NKT cells. The thermotropic behavior and structure of SF dispersions and its mixtures (4.8-16.6 mol %) with cationic dioctadecyldimethylammonium bromide (DODAB) bilayers were investigated by differential scanning calorimetry and electron paramagnetic resonance spectroscopy. The non-interdigitated lamellar structures formed by pure SF display broad thermal events around 27.5 °C when heated and cooled. These events disappear upon mixing with DODAB, showing complete lipid miscibility. SF decreases the DODAB gel-phase packing, with a consequent decrease in phase-transition temperatures and cooperativity upon heating. In contrast, SF increases the rigidity of the DODAB fluid phase, resulting in a smaller decrease in transition temperatures upon cooling. The hysteresis between heating and cooling decreased as the SF molar fraction increased. These effects on DODAB are similar to the ones described for other glycolipids, such as αGalCer and βGlcCer. This might be due to the orientation of the rigid and planar amide bond that connects their sphingoid bases and acyl chains, which result in a V-shaped conformation of the glycolipid molecules. The current results may be important to plan and develop new immunotherapeutic tools based on SF.
C24:1 硫酸脑苷脂(SF)是II型自然杀伤T细胞的内源性激活剂。通过差示扫描量热法和电子顺磁共振光谱研究了SF分散体及其与阳离子二辛基二甲基溴化铵(DODAB)双层混合物(4.8 - 16.6摩尔%)的热致行为和结构。纯SF形成的非交错层状结构在加热和冷却时在27.5°C左右显示出宽泛的热事件。与DODAB混合后这些事件消失,表明脂质完全互溶。SF降低了DODAB凝胶相堆积,导致加热时相变温度和协同性降低。相反,SF增加了DODAB流体相的刚性,导致冷却时相变温度下降较小。随着SF摩尔分数增加,加热和冷却之间的滞后减小。这些对DODAB的影响与其他糖脂(如α半乳糖神经酰胺和β葡萄糖神经酰胺)所描述的影响相似。这可能是由于连接其鞘氨醇碱基和酰基链的刚性平面酰胺键的取向,导致糖脂分子呈V形构象。目前的结果对于基于SF规划和开发新的免疫治疗工具可能很重要。