Ibuprofen and the Phosphatidylcholine Bilayer: Membrane Water Permeability in the Presence and Absence of Cholesterol
Ibuprofen and the Phosphatidylcholine Bilayer: Membrane Water Permeability in the Presence and Absence of Cholesterol
复制标题
布洛芬和磷脂酰胆碱双层：存在和不存在胆固醇时的膜水渗透性
DOI：
10.1021/acs.langmuir.0c03638
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发表时间：
2021
期刊：
影响因子：
3.9
通讯作者：
Lee, Sunghee
中科院分区：
文献类型：
--
作者：
Wood, Megan;Morales, Michael;Miller, Elizabeth;Braziel, Samuel;Giancaspro, Joseph;Scollan, Patrick;Rosario, Juan;Gayapa, Alyssa;Krmic, Michael;Lee, Sunghee
药物与细胞膜之间的相互作用可以调节细胞膜的结构和物理性质。由此产生的膜完整性的扰动可能会影响插入膜内的蛋白质的构象，干扰膜宿主的生物功能。在这项研究中，液滴界面双层（DIB），模型细胞膜，用于检查布洛芬，非甾体抗炎药（NSAID），对transbilayer水渗透性，这是一个基本的膜生物物理特性的影响。我们的研究结果表明，中性布洛芬（pH 3）的存在下，增加了由1，2-二油酰基-sn-甘油-3-磷酸胆碱（DOPC）的脂质膜的水渗透性。然而，当胆固醇与DOPC一起存在时，无论DOPC中胆固醇含量如何，加入布洛芬都不会影响透水性。考虑到胆固醇通常被认为会影响烃链区域中的堆积，我们的研究结果表明布洛芬分子和胆固醇对磷脂组装体的烃核心环境的相反作用之间的潜在竞争可能会影响整体水运输现象。共焦拉曼显微光谱和界面张力测定的结果表明，布洛芬分子诱导DOPC脂质双层的结构和动力学的变化。这些结果表明，布洛芬的存在增加了纯DOPC的透水性，但不是DOPC-胆固醇混合物的透水性，提供了对代表性NSAID对异质生物膜的差异效应的了解，这取决于局部组成和结构，结果将表明对这些分子诱导的胃肠道损伤和毒性的理解增加。
The interactions between drugs and cell membranes can modulate the structural and physical properties of membranes. The resultant perturbations of the membrane integrity may affect the conformation of the proteins inserted within the membrane, disturbing the membrane-hosted biological functions. In this study, the droplet interface bilayer (DIB), a model cell membrane, is used to examine the effects of ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), on transbilayer water permeability, which is a fundamental membrane biophysical property. Our results indicate that the presence of neutral ibuprofen (pH 3) increases the water permeability of the lipid membranes composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). When cholesterol is present with the DOPC, however, the water permeability is not influenced by addition of ibuprofen, regardless of the cholesterol content in DOPC. Given the fact that cholesterol is generally considered to impact packing in the hydrocarbon chain regions, our findings suggest that a potential competition between opposing effects of ibuprofen molecules and cholesterol on the hydrocarbon core environment of the phospholipid assembly may influence the overall water transport phenomena. Results from confocal Raman microspectroscopy and interfacial tensiometry show that ibuprofen molecules induce substantial structural and dynamic changes in the DOPC lipid bilayer. These results, demonstrating that the presence of ibuprofen increases the water permeability of pure DOPC but not that of DOPC–cholesterol mixtures, provide insight into the differential effect of a representative NSAID on heterogeneous biological membranes, depending upon the local composition and structure, results which will signal increased understanding of the gastrointestinal damage and toxicity induced by these molecules.