Grzegorz Łazarski, Natan Rajtar, Agata Żak, Dorota Jamróz, Mariusz Kepczynski
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引用次数: 0
Abstract
Chondroitin sulfates (CSs) are important components of the extracellular matrix and side chains of membrane proteoglycans. These polysaccharides are, therefore, likely to interact with plasma membranes and play a significant role in modulating cellular functions. So far, the details of the processes occurring at the interface between the extracellular matrix and cellular membranes are not fully understood. In this study, we used experimental methods and atomic-scale molecular dynamics (MD) simulations to reveal the molecular picture of the interactions between CS and phosphocholine (PC) membranes, used as a simplified model of cell membranes. MD simulations reveal that the polysaccharide associates to the PC bilayer as a result of electrostatic interactions between the positively charged quaternary ammonium groups of choline and the negatively charged sulfate groups of CS. Compared to an aqueous medium, the adsorbed polysaccharide chains adopt more elongated conformations, which facilitates the electrostatic interactions with the membrane, and have a high degree of freedom to change their conformations and to adhere to and detach from the membrane surface. Penetrating slightly between the polar groups of the bilayer, they form a loosely anchored layer, but do not intrude into the hydrophobic region of the PC bilayer. The CS adsorption spread the PC headgroups apart, which is manifested by an increase in the value of the area pre lipid. The expansion of the lipid polar groups weakens the dispersion interactions between the lipid acyl chains. As a result, the lipid membrane in the membrane-polysaccharide contact areas becomes more fluid. Our outcomes may help to understand in detail the interaction of chondroitin sulfate with zwitterionic membranes at the molecular level, which is of biological interest since many biological processes depend on lipid-CS interactions.
硫酸软骨素(CS)是细胞外基质的重要成分,也是膜蛋白多糖的侧链。因此,这些多糖很可能与质膜相互作用,并在调节细胞功能方面发挥重要作用。迄今为止,人们尚未完全了解细胞外基质与细胞膜之间界面过程的细节。在这项研究中,我们利用实验方法和原子尺度的分子动力学(MD)模拟揭示了 CS 与磷脂酰胆碱(PC)膜(用作细胞膜的简化模型)之间相互作用的分子图景。MD 模拟显示,由于胆碱带正电的季铵基团和 CS 带负电的硫酸基团之间的静电作用,多糖与 PC 双层结合。与水介质相比,被吸附的多糖链采用了更多的拉长构象,这有利于与膜发生静电作用,并且具有很高的自由度来改变其构象,粘附或脱离膜表面。它们略微穿透双分子层的极性基团,形成一个松散的固定层,但不会侵入 PC 双分子层的疏水区域。CS 吸附会使 PC 头基分开,表现为脂前面积值的增加。脂质极性基团的扩大削弱了脂质酰基链之间的分散相互作用。因此,膜-多糖接触区的脂膜变得更加流动。我们的研究结果可能有助于在分子水平上详细了解硫酸软骨素与齐聚物膜的相互作用,这具有生物学意义,因为许多生物过程都依赖于脂质-CS 的相互作用。
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.