Anesthetics significantly increase the amount of intramembrane water in lipid membranes
Anesthetics significantly increase the amount of intramembrane water in lipid membranes
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DOI：
10.1039/d0sm01271h
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发表时间：
2020-11-14
期刊：
影响因子：
3.4
通讯作者：
Rheinstadter, Maikel C.
中科院分区：
文献类型：
--
作者：
Himbert, Sebastian;Zhang, Lili;Rheinstadter, Maikel C.
Meyer和Overton认为，麻醉的效力与药物分子在细胞膜中的分配直接相关。许多分子与脂质双分子层相互作用，导致结构和功能的变化。这仍然是一个悬而未决的问题，膜性质的变化是负责潜在的麻醉效果，或者如果麻醉剂的作用是通过结合直接目标。采用全原子分子动力学模拟和中子衍射实验相结合的方法，研究了乙醇、乙醚和异氟醚对脂质双分子层水分分布的影响。模拟结果表明，乙醇、乙醚和异氟醚的膜-药物相互作用较强，分配系数分别为38%、92%和100%，并为膜核中水的分配增加提供了证据。在中子衍射实验中，通过选择性氘标记脂类、麻醉药物和水分子来测定膜内水分子的数量。在乙醇的存在下，每个脂质增加了4个水分子。发现乙醚和异氟醚显著增加膜内水量25%（8个水分子）。这种膜内水的增加可能有助于麻醉药和脂质膜之间的非特异性相互作用。
The potency of anesthesia was directly linked to the partitioning of the drug molecules in cell membranes by Meyer and Overton. Many molecules interact with lipid bilayers and lead to structural and functional changes. It remains an open question which change in membrane properties is responsible for a potential anesthetic effect or if anesthetics act by binding to direct targets. We studied the effect of ethanol, diethyl ether and isoflurane on the water distribution in lipid bilayers by combining all-atom molecular dynamics simulations and neutron diffraction experiments. The simulations show strong membrane-drug interactions with partitioning coefficients of 38%, 92% and 100% for ethanol, diethyl ether and isoflurane, respectively, and provide evidence for an increased water partitioning in the membrane core. The amount of intramembrane water molecules was experimentally determined by selectively deuterium labeling lipids, anesthetic drug and water molecules in neutron diffraction experiments. Four additional water molecules per lipid were observed in the presence of ethanol. Diethyl ether and isoflurane were found to significantly increase the amount of intramembrane water by 25% (8 water molecules). This increase in intramembrane water may contribute to the non-specific interactions between anesthetics and lipid membranes.