Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion.
Interplay Between Receptor-Ligand Binding and Lipid Domain Formation Depends on the Mobility of Ligands in Cell-Substrate Adhesion.
复制标题
受体-配体结合和脂质结构域形成之间的相互作用取决于细胞-基质粘附中配体的迁移率
DOI：
10.3389/fmolb.2021.655662
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发表时间：
2021
影响因子：
5
通讯作者：
Song F
中科院分区：
文献类型：
--
作者：
Li L;Wang X;Wu H;Shao Y;Wu H;Song F
细胞与细胞的粘附和细胞与细胞外基质的粘附是由细胞膜上的受体与相对表面的同源配体的特异性结合介导的。黏附受体可以对细胞膜上形成的纳米级脂质团簇表现出亲和力。这种粘附系统的实验研究通常涉及细胞粘附在具有固定配体的固体表面或具有移动配体的支撑脂质双分子层上。这些细胞-底物粘附的一个核心问题是配体的移动性如何物理影响它们与粘附受体的结合，从而影响与受体相关的纳米级脂质团簇的行为。利用统计力学模型和蒙特卡罗模拟配体细胞与底物的粘附，我们发现，对于移动配体，与粘附受体的结合可以促进中尺度脂质结构域的形成，从而增强受体与配体的结合。然而，在固定配体的情况下，受体与配体的结合以及纳米级脂质团簇进一步聚结的趋势取决于配体在底物上的分布。我们的发现有助于解释为什么不同的粘附实验，以确定受体-配体结合和细胞膜异质性之间的相互作用，导致矛盾的结果。
Cell-cell adhesion and the adhesion of cells to extracellular matrix are mediated by the specific binding of receptors on the cell membrane to their cognate ligands on the opposing surface. The adhesion receptors can exhibit affinity for nanoscale lipid clusters that form in the cell membrane. Experimental studies of such adhesion systems often involve a cell adhering either to a solid surface with immobile ligands or a supported lipid bilayer with mobile ligands. A central question in these cell-substrate adhesions is how the mobility of the ligands physically affects their binding to the adhesion receptors and thereby the behavior of the nanoscale lipid clusters associated with the receptors. Using a statistical mechanical model and Monte Carlo simulations for the adhesion of cells to substrates with ligands, we find that, for mobile ligands, binding to adhesion receptors can promote the formation of mesoscale lipid domains, which in turn enhances the receptor-ligand binding. However, in the case of immobile ligands, the receptor-ligand binding and the tendency for the nanoscale lipid clusters to further coalesce depend on the distribution of the ligands on the substrate. Our findings help to explain why different adhesion experiments for identifying the interplay between receptor-ligand binding and heterogeneities in cell membranes led to contradictory results.