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.
摘要：
硫酸软骨素（CSs）是细胞外基质和膜蛋白聚糖侧链的重要成分。这些多糖是，因此,可能与质膜相互作用，并在调节细胞功能中起重要作用。到目前为止,细胞外基质和细胞膜之间的界面发生的过程的细节还没有完全理解。在这项研究中,我们使用实验方法和原子尺度分子动力学（MD）模拟来揭示CS和磷酸胆碱（PC）膜之间相互作用的分子图，用作细胞膜的简化模型。MD模拟表明，由于胆碱的带正电的季铵基团和CS的带负电的硫酸根之间的静电相互作用，多糖与PC双层缔合。与水性介质相比，吸附的多糖链采用更细长的构象，这促进了与膜的静电相互作用，并且具有高度的自由度来改变它们的构象以及粘附到膜表面和从膜表面分离。在双层的极性基团之间轻微渗透，它们形成松散锚定的层，但不侵入PC双层的疏水区域。CS吸附使PC头基团分开，这表现为面积前脂质的值增加。脂质极性基团的膨胀削弱了脂质酰基链之间的分散相互作用。因此,膜-多糖接触区域中的脂质膜变得更加流体。我们的结果可能有助于详细了解硫酸软骨素与两性离子膜在分子水平上的相互作用，这具有生物学意义,因为许多生物过程依赖于脂质-CS相互作用。
