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研究 - 醇对脂类运动的截止效应:一项生物物理研究。

Investigating the cut-off effect of -alcohols on lipid movement: a biophysical study.

机构信息

Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.

NIST Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD, USA.

出版信息

Soft Matter. 2023 Jul 5;19(26):5001-5015. doi: 10.1039/d2sm01583h.

Abstract

Cellular membranes are responsible for absorbing the effects of external perturbants for the cell's survival. Such perturbants include small ubiquitous molecules like -alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of -alcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TR-SANS), small angle X-ray scattering (SAXS), all atomistic and coarse-grained molecular dynamics (MD) simulations, and calcein leakage assays. At an alcohol concentration of 30 mol% of the overall lipid content, TR-SANS showed 1-hexanol (C6OH) increased transverse lipid diffusion, flip-flop. As alcohol chain length increased from C6 to C10 and longer, lipid flip-flop slowed by factors of 5.6 to 32.2. Intervesicular lipid exchange contrasted these results with only a slight cut-off at alcohol concentrations of 30 mol% but not 10 mol%. SAXS, MD simulations, and leakage assays revealed changes to key bilayer properties, such as bilayer thickness and fluidity, that correlate well with the effects on lipid flip-flop rates. Finally, we tie our results to a defect-mediated pathway for alcohol-induced lipid flip-flop.

摘要

细胞膜负责吸收细胞生存所需的外部扰动因素的影响。这些扰动因素包括像醇这样的普遍存在的小分子,它们被观察到具有麻醉能力,这种效应在醇链长度的截止处逐渐减弱。为了解释这种截止效应,并补充先前的生化研究,我们研究了一系列 - 醇(碳链长度为 2-18)及其对几种双层性质的影响,包括脂质翻转、囊泡间交换、扩散、膜弯曲刚性等。为此,我们采用了一系列生物物理技术,如时间分辨小角中子散射(TR-SANS)、小角 X 射线散射(SAXS)、全原子和粗粒分子动力学(MD)模拟以及钙黄绿素渗漏测定。在醇浓度为总脂质含量的 30 mol%时,TR-SANS 显示 1-己醇(C6OH)增加了横向脂质扩散和翻转。随着醇链长度从 C6 增加到 C10 及更长,脂质翻转的速度减慢了 5.6 到 32.2 倍。囊泡间脂质交换与这些结果形成对比,仅在醇浓度为 30 mol%而不是 10 mol%时出现轻微截止。SAXS、MD 模拟和渗漏测定揭示了关键双层性质的变化,如双层厚度和流动性,这些性质与脂质翻转速率的变化密切相关。最后,我们将我们的结果与缺陷介导的醇诱导脂质翻转途径联系起来。

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