Kav Batuhan, Grafmüller Andrea, Schneck Emanuel, Weikl Thomas R
Max Planck Institute of Colloids and Interfaces, Department of Theory and Bio-Systems, Am Mühlenberg 1, 14476 Potsdam, Germany.
Max Planck Institute of Colloids and Interfaces, Department of Biomaterials, Am Mühlenberg 1, 14476 Potsdam, Germany and Technische Universität Darmstadt, Physics Department, Hochschulstraße 8, 64289 Darmstadt, Germany.
Nanoscale. 2020 Aug 28;12(33):17342-17353. doi: 10.1039/d0nr03696j.
Carbohydrates such as the trisaccharide motif LeX are key constituents of cell surfaces. Despite intense research, the interactions between carbohydrates of apposing cells or membranes are not well understood. In this article, we investigate carbohydrate-carbohydrate interactions in membrane adhesion as well as in solution with extensive atomistic molecular dynamics simulations that exceed the simulation times of previous studies by orders of magnitude. For LeX, we obtain association constants of soluble carbohydrates, adhesion energies of lipid-anchored carbohydrates, and maximally sustained forces of carbohydrate complexes in membrane adhesion that are in good agreement with experimental results in the literature. Our simulations thus appear to provide a realistic, detailed picture of LeX-LeX interactions in solution and during membrane adhesion. In this picture, the LeX-LeX interactions are fuzzy, i.e. LeX pairs interact in a large variety of short-lived, bound conformations. For the synthetic tetrasaccharide Lac 2, which is composed of two lactose units, we observe similarly fuzzy interactions and obtain association constants of both soluble and lipid-anchored variants that are comparable to the corresponding association constants of LeX. The fuzzy, weak carbohydrate-carbohydrate interactions quantified in our simulations thus appear to be a generic feature of small, neutral carbohydrates such as LeX and Lac 2.
诸如三糖基序LeX这样的碳水化合物是细胞表面的关键组成部分。尽管进行了深入研究，但相邻细胞或膜的碳水化合物之间的相互作用仍未得到很好的理解。在本文中，我们通过广泛的原子分子动力学模拟研究了膜黏附中以及溶液中的碳水化合物 - 碳水化合物相互作用，这些模拟的时间尺度比以前的研究超出了几个数量级。对于LeX，我们获得了可溶性碳水化合物的缔合常数、脂质锚定碳水化合物的黏附能以及膜黏附中碳水化合物复合物的最大持续力，这些结果与文献中的实验结果高度一致。因此，我们的模拟似乎提供了溶液中以及膜黏附过程中LeX - LeX相互作用的真实、详细图景。在此图景中，LeX - LeX相互作用是模糊的，即LeX对以多种短寿命的结合构象相互作用。对于由两个乳糖单元组成的合成四糖Lac 2，我们观察到类似的模糊相互作用，并获得了可溶性和脂质锚定变体的缔合常数，这些常数与LeX的相应缔合常数相当。因此，我们模拟中量化的模糊、弱碳水化合物 - 碳水化合物相互作用似乎是诸如LeX和Lac 2等小型中性碳水化合物的一个普遍特征。
