Evidence for capture of spin-labeled ibuprofen drug molecules by lipid rafts in model membranes

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemistry and Physics of Lipids Pub Date : 2024-11-02 DOI:10.1016/j.chemphyslip.2024.105450

Elena A. Golysheva, Denis S. Baranov, Sergei A. Dzuba

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引用次数: 0

Abstract

Lipid rafts are lipid-cholesterol nanostructures thought to exist in cell membranes, which are characterized by higher ordering compared to their surroundings. Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) have a high affinity for phospholipid membranes and can alter their structure and biological properties. Here we use electron paramagnetic resonance (EPR) in its pulsed electron spin echo (ESE) version to study spin-labeled ibuprofen (ibuprofen-SL) in a raft-mimicking bilayer, which consists of an equimolar mixture of the phospholipids dioleoyl-glycero-phosphocholine (DOPC) and dipalmitoyl-glycero-phosphocholine (DPPC), with cholesterol added in various proportions. ESE decays are sensitive to the presence of low-temperature small-angle orientational motions of molecules − stochastic molecular librations. The data obtained show that in the presence of lipid rafts the temperature dependence of the spin relaxation rate induced by this motion reaches a plateau. This behavior is characteristic of non-cooperative motion of a molecule bound to some structure denser than the rest of the medium. Based on this analogy, the data obtained were interpreted as evidence that ibuprofen-SL molecules are adsorbed on the raft boundaries.

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自旋标记的布洛芬药物分子被模型膜中的脂质筏捕获的证据。

脂质筏是一种被认为存在于细胞膜中的脂质-胆固醇纳米结构，其特点是与周围环境相比具有更高的有序性。布洛芬和其他非甾体抗炎药（NSAIDs）对磷脂膜有很高的亲和力，能改变磷脂膜的结构和生物特性。在这里，我们使用脉冲电子自旋回波（ESE）版本的电子顺磁共振（EPR）来研究筏状模拟双分子层中的自旋标记布洛芬（布洛芬-SL），筏状模拟双分子层是由二油酰-甘油-磷脂胆碱（DOPC）和二棕榈酰-甘油-磷脂胆碱（DPPC）的等摩尔混合物以及不同比例的胆固醇组成。ESE 衰减对分子的低温小角度定向运动--随机分子自由度--的存在很敏感。获得的数据表明，在脂质筏存在的情况下，由这种运动引起的自旋弛豫速率的温度依赖性达到了一个高点。这种行为是表面结合分子非合作运动的特征。根据这一类比，所获得的数据被解释为布洛芬-SL 分子吸附在脂筏边界上的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chemistry and Physics of Lipids 生物-生化与分子生物学

CiteScore

7.60

自引率

2.90%

发文量

审稿时长

40 days

期刊介绍： Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.