Binding constant of cell adhesion receptors and substrate-immobilized ligands depends on the distribution of ligands
Binding constant of cell adhesion receptors and substrate-immobilized ligands depends on the distribution of ligands
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细胞粘附受体和底物固定配体的结合常数取决于配体的分布
DOI：
10.1103/physreve.97.012405
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发表时间：
2018-01-16
影响因子：
2.4
通讯作者：
Song, Fan
中科院分区：
文献类型：
--
作者：
Li, Long;Hu, Jinglei;Song, Fan
细胞-细胞粘附以及细胞与组织和细胞外基质的粘附是免疫应答、组织发育和细胞运动的关键，其敏感地依赖于锚定在相对表面上的受体和配体分子的结合常数。一个重要的问题仍然是固定化的配体是否影响与细胞粘附受体结合的亲和力。我们已经研究了粘附多组分膜与固定配体涂覆的平面基板使用Monte Carlo模拟的统计介观模型与生物相关的参数。我们发现，粘附受体与固定在基板上的配体的结合受到配体分布的强烈影响。在配体簇的情况下，受体-配体结合常数可以显著增强，这是由于在形成额外的复合物时，模型细胞膜中的脂筏结构域的翻译熵损失较少。对于随机或均匀地固定在基板上的配体，结合常数是相当减少，因为定位在脂筏域的受体必须支付能量的罚款，以结合配体。我们的研究结果有助于理解为什么细胞基质粘附实验测量脂筏对受体-配体相互作用的影响导致矛盾的结果。
Cell-cell adhesion and the adhesion of cells to tissues and extracellular matrix, which are pivotal for immune response, tissue development, and cell locomotion, depend sensitively on the binding constant of receptor and ligand molecules anchored on the apposing surfaces. An important question remains of whether the immobilization of ligands affects the affinity of binding with cell adhesion receptors. We have investigated the adhesion of multicomponent membranes to a flat substrate coated with immobile ligands using Monte Carlo simulations of a statistical mesoscopic model with biologically relevant parameters. We find that the binding of the adhesion receptors to ligands immobilized on the substrate is strongly affected by the ligand distribution. In the case of ligand clusters, the receptor-ligand binding constant can be significantly enhanced due to the less translational entropy loss of lipid-raft domains in the model cell membranes upon the formation of additional complexes. For ligands randomly or uniformly immobilized on the substrate, the binding constant is rather decreased since the receptors localized in lipid-raft domains have to pay an energetic penalty in order to bind ligands. Our findings help to understand why cell-substrate adhesion experiments for measuring the impact of lipid rafts on the receptor-ligand interactions led to contradictory results.