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How the replacement of cholesterol by 25-hydroxycholesterol affects the interactions with sphingolipids: The Langmuir Monolayer Study complemented with theoretical calculations
Journal of The Royal Society Interface ( IF 3.9 ) Pub Date : 2021-03-17 , DOI: 10.1098/rsif.2021.0050
Jan Kobierski 1 , Anita Wnętrzak 2 , Anna Chachaj-Brekiesz 2 , Anna Filiczkowska 3 , Aneta D Petelska 4 , Patrycja Dynarowicz-Latka 2
Affiliation  

In this paper, a representative of chain-oxidized sterols, 25-hydroxycholesterol (25-OH), has been studied in Langmuir monolayers mixed with the sphingolipids sphingomyelin (SM) and ganglioside (GM1) to build lipid rafts. A classical Langmuir monolayer approach based on thermodynamic analysis of interactions was complemented with microscopic visualization of films (Brewster angle microscopy), surface-sensitive spectroscopy (polarization modulation–infrared reflection–absorption spectroscopy) and theoretical calculations (density functional theory modelling and molecular dynamics simulations). Strong interactions between 25-OH and both investigated sphingolipids enabled the formation of surface complexes. As known from previous studies, 25-OH in pure monolayers can be anchored to the water surface with a hydroxyl group at either C(3) or C(25). In this study, we investigated how the presence of additional strong interactions with sphingolipids modifies the surface arrangement of 25-OH. Results have shown that, in the 25-OH/GM1 system, there are no preferences regarding the orientation of the 25-OH molecule in surface complexes and two types of complexes are formed. On the other hand, SM enforces one specific orientation of 25-OH: being anchored with the C(3)–OH group to the water. The strength of interactions between the studied sphingolipids and 25-OH versus cholesterol is similar, which indicates that cholesterol may well be replaced by oxysterol in the lipid raft system. In this way, the composition of lipid rafts can be modified, changing their rheological properties and, as a consequence, influencing their proper functioning.



中文翻译:

用 25-羟基胆固醇替代胆固醇如何影响与鞘脂的相互作用:朗缪尔单层研究与理论计算相辅相成

在本文中,在与鞘磷脂 (SM) 和神经节苷脂 (GM 1) 构建脂筏。基于相互作用的热力学分析的经典朗缪尔单层方法与薄膜的显微可视化(布鲁斯特角显微镜)、表面敏感光谱(偏振调制-红外反射-吸收光谱)和理论计算(密度泛函理论建模和分子动力学模拟)相辅相成)。25-OH 和两种研究的鞘脂之间的强相互作用使表面复合物的形成成为可能。从以前的研究中得知,纯单层中的 25-OH 可以用 C(3) 或 C(25) 处的羟基固定在水面上。在这项研究中,我们研究了与鞘脂的额外强相互作用如何改变 25-OH 的表面排列。结果表明,在 25-OH/GM在图1体系中,表面配合物中 25-OH 分子的取向没有偏好,形成了两种配合物。另一方面,SM 强制 25-OH 的一个特定方向:与 C(3)-OH 基团固定在水中。所研究的鞘脂和 25-OH 与胆固醇之间的相互作用强度相似,这表明胆固醇很可能在脂筏系统中被氧甾醇取代。通过这种方式,可以改变脂筏的组成,改变它们的流变特性,从而影响它们的正常功能。

更新日期:2021-03-17
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