The nanoscopic layer of water that directly hydrates biological membranes plays a critical role in maintaining the cell structure, regulating biochemical processes, and managing intermolecular interactions at the membrane interface. Therefore, comprehending the membrane structure, including its hydration, is essential for understanding the chemistry of life. While cholesterol is a fundamental lipid molecule in mammalian cells, influencing both the structure and dynamics of cell membranes, its impact on the structure of interfacial water has remained unknown. We used surface-specific vibrational sum-frequency generation spectroscopy to study the effect of cholesterol on the structure and hydration of monolayers of the lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and egg sphingomyelin (SM). We found that for the unsaturated lipid DOPC, cholesterol intercalates in the membrane without significantly changing the orientation of the lipid tails and the orientation of the water molecules hydrating the headgroups of DOPC. In contrast, for the saturated lipids DPPC and SM, the addition of cholesterol leads to clearly enhanced packing and ordering of the hydrophobic tails. It is also observed that the orientation of the water hydrating the lipid headgroups is enhanced upon the addition of cholesterol. These results are important because the orientation of interfacial water molecules influences the cell membranes’ dipole potential and the strength and specificity of interactions between cell membranes and peripheral proteins and other biomolecules. The lipid nature-dependent role of cholesterol in altering the arrangement of interfacial water molecules offers a fresh perspective on domain-selective cellular processes, such as protein binding.

中文翻译：

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胆固醇改变模型细胞膜中的界面水排列

直接水合生物膜的纳米级水层在维持细胞结构、调节生化过程和管理膜界面分子间相互作用方面发挥着关键作用。因此，理解膜结构，包括其水合作用，对于理解生命的化学至关重要。虽然胆固醇是哺乳动物细胞中的基本脂质分子，影响细胞膜的结构和动力学，但其对界面水结构的影响仍然未知。我们使用表面特异性振动和频发生光谱来研究胆固醇对脂质 1,2-二棕榈酰- sn -甘油-3-磷酸胆碱 (DPPC)、1,2-二油酰- sn-甘油-3-磷酸胆碱 (DOPC) 和鸡蛋鞘磷脂 (SM)。我们发现，对于不饱和脂质 DOPC，胆固醇嵌入膜中，而不会显着改变脂质尾部的方向和水合 DOPC 头基的水分子的方向。相比之下，对于饱和脂质 DPPC 和 SM，胆固醇的添加导致疏水尾部的堆积和排序明显增强。还观察到，添加胆固醇后，水合脂质头基的水的取向得到增强。这些结果很重要，因为界面水分子的方向影响细胞膜的偶极电位以及细胞膜与外周蛋白质和其他生物分子之间相互作用的强度和特异性。胆固醇在改变界面水分子排列方面的脂质性质依赖性作用为域选择性细胞过程（例如蛋白质结合）提供了新的视角。