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The influence of an antitumor lipid - erucylphosphocholine - on artificial lipid raft system modeled as Langmuir monolayer.
Molecular Membrane Biology ( IF 2.857 ) Pub Date : 2016-02-25 , DOI: 10.3109/09687688.2015.1125537
Anita Wnętrzak 1 , Kazimierz Łątka 1 , Katarzyna Makyła-Juzak 2 , Joanna Zemla 1 , Patrycja Dynarowicz-Łątka 2
Affiliation  

Outer layer of cellular membrane contains ordered domains enriched in cholesterol and sphingolipids, called ‘lipid rafts’, which play various biological roles, i.e., are involved in the induction of cell death by apoptosis. Recent studies have shown that these domains may constitute binding sites for selected drugs. For example alkylphosphocholines (APCs), which are new-generation antitumor agents characterized by high selectivity and broad spectrum of activity, are known to have their molecular targets located at cellular membrane and their selective accumulation in tumor cells has been hypothesized to be linked with the alternation of biophysical properties of lipid rafts. To get a deeper insight into this issue, interactions between representative APC: erucylphosphocholine, and artificial lipid raft system, modeled as Langmuir monolayer (composed of cholesterol and sphingomyelin mixed in 1:2 proportion) were investigated. The Langmuir monolayer experiments, based on recording surface pressure-area isotherms, were complemented with Brewster angle microscopy results, which enabled direct visualization of the monolayers structure. In addition, the investigated monolayers were transferred onto solid supports and studied with AFM. The interactions between model raft system and erucylphosphocholine were analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ΔGexc function). The obtained results indicate that erucylphosphocholine introduced to raft-mimicking model membrane causes fluidizing effect and weakens the interactions between cholesterol and sphingomyelin, which results in phase separation at high surface pressures. This leads to the redistribution of cholesterol molecules in model raft, which confirms the results observed in biological studies.



中文翻译:

抗肿瘤脂质-芥酸磷酸胆碱-对模拟为Langmuir单层的人工脂质筏系统的影响。

细胞膜的外层含有富含胆固醇和鞘脂的有序域,称为“脂质筏”,它们起着各种生物学作用,即参与通过凋亡诱导细胞死亡。最近的研究表明,这些结构域可能构成所选药物的结合位点。例如,烷基磷酸胆碱(APC)是具有高度选择性和广谱活性的特征的新一代抗肿瘤药物,已知其分子靶标位于细胞膜上,并且假设它们在肿瘤细胞中的选择性积累与肿瘤细胞的生长有关。脂筏的生物物理特性的交替。为了更深入地了解这个问题,代表性的APC:芥子酰磷酸胆碱和人工脂质筏系统之间的相互作用,建模为Langmuir单层模型(由胆固醇和鞘磷脂按1:2比例混合组成)进行了研究。基于记录表面压力-面积等温线的Langmuir单层实验与Brewster角度显微镜结果相辅相成,可以直接观察单层结构。另外,将研究的单层转移到固体载体上并用AFM研究。定性(具有平均分子面积值)和定量(具有ΔG)分析了模型筏系统与芥子酰磷酸胆碱之间的相互作用 可以直接可视化单层结构。另外,将研究的单层转移到固体载体上并用AFM研究。定性(具有平均分子面积值)和定量(具有ΔG)分析了模型筏系统与芥子酰磷酸胆碱之间的相互作用 可以直接可视化单层结构。另外,将研究的单层转移到固体载体上并用AFM研究。定性(具有平均分子面积值)和定量(具有ΔG)分析了模型筏系统与芥子酰磷酸胆碱之间的相互作用排除功能)。获得的结果表明,向筏模拟模型膜中引入的芥子酰磷酸胆碱会引起流化作用,并削弱胆固醇与鞘磷脂之间的相互作用,从而导致在高表面压力下发生相分离。这导致胆固醇在模型筏中的重新分布,这证实了生物学研究中观察到的结果。

更新日期:2016-02-25
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