Baek Ji Min, Jung Woo Hyuk, Yu Eui-Sang, Ahn Dong June, Ryu Yong-Sang
Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Department of Chemical and Biological Engineering, Korea University, Seoul 02841, Republic of Korea.
J Am Chem Soc. 2022 Dec 7;144(48):21887-21896. doi: 10.1021/jacs.2c06626. Epub 2022 Nov 11.
Passive water penetration across the cell membrane by osmotic diffusion is essential for the homeostasis of cell volume, in addition to the protein-assisted active transportation of water. Since membrane components can regulate water permeability, controlling compositional variation during the volume regulatory process is a prerequisite for investigating the underlying mechanisms of water permeation and related membrane dynamics. However, the lack of a viable in vitro membrane platform in hypertonic solutions impedes advanced knowledge of cell volume regulation processes, especially cholesterol-enriched lipid domains called lipid rafts. By reconstituting the liquid-ordered (L) domain as a likeness of lipid rafts, we verified suppressed water permeation across the L domains, which had yet to be confirmed with experimental demonstrations despite a simulation approach. With the help of direct transfer of the L domains from vesicles to supported lipid membranes, the biological roles of lipid composition in suppressed water translocation were experimentally confirmed. Additionally, the improvement in membrane stability under hypertonic conditions was demonstrated based on molecular dynamics simulations.
除了蛋白质辅助的水主动运输外，通过渗透扩散实现的被动水跨细胞膜渗透对于细胞体积的稳态至关重要。由于膜成分可以调节水渗透性，因此在体积调节过程中控制成分变化是研究水渗透的潜在机制和相关膜动力学的先决条件。然而，缺乏在高渗溶液中可行的体外膜平台阻碍了对细胞体积调节过程的深入了解，特别是对称为脂筏的富含胆固醇的脂质结构域的了解。通过将液晶相（L）结构域重构为脂筏的类似物，我们证实了跨L结构域的水渗透受到抑制，尽管有模拟方法，但这一点尚未得到实验证明。借助于将L结构域从囊泡直接转移到支撑脂质膜上，实验证实了脂质组成在抑制水转运中的生物学作用。此外，基于分子动力学模拟证明了高渗条件下膜稳定性的提高。
