Simulations of cell-surface integrin binding to nanoscale-clustered adhesion ligands
Simulations of cell-surface integrin binding to nanoscale-clustered adhesion ligands
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DOI：
10.1016/s0006-3495(02)75379-4
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发表时间：
2002-01-01
影响因子：
3.4
通讯作者：
Griffith, LG
中科院分区：
文献类型：
--
作者：
Irvine, DJ;Hue, KA;Griffith, LG
连接的整联蛋白的聚集强烈影响整联蛋白信号传导和整联蛋白与细胞内结构之间的机械连接。整联蛋白配体在簇中的细胞外空间组织可以促进结合的整联蛋白的聚集，从而潜在地调节细胞对细胞外环境中限定的平均量的配体的应答。这种配体聚集效应在控制整体受体占用率的可能作用在这里研究使用一个简单的质量作用平衡模型，以及一个二维的Monte Carlo晶格描述的细胞-基质界面，其中细胞表面受体是自由扩散的界面的平面中，并与基板固定的配体相互作用。从分析处理和模拟数据的结果表明，对于受体-配体结合平衡不受相邻复合物的影响的单态模型，配体的聚集不会增强总受体结合。然而，如果受体结合能在相邻连接受体的存在下增加，则出现强配体空间分布效应。增加配体密度的非线性响应也观察到，即使在随机配体的位置，由于随机并列的配体分子的情况下。这些结果描述了如何由细胞外基质或合成的仿生材料的配体的空间分布可能控制细胞对外部配体的反应，并提出了一种反馈机制，通过该机制可能会引发局部接触形成。
Clustering of ligated integrins strongly influences integrin signaling and mechanical linkages between integrins and intracellular structures. Extracellular spatial organization of integrin ligands in clusters may facilitate clustering of bound integrins and thus potentially regulate cellular responses to a defined average amount of ligand in the extracellular environment. The possible role of such ligand clustering effects in controlling overall receptor occupancy is studied here using a simple mass-action equilibrium model as well as a two-dimensional Monte Carlo lattice description of the cell-substrate interface, where cell surface receptors are free to diffuse in the plane of the interface and interact with the substrate-immobilized ligand. Results from the analytical treatment and simulation data indicate that for a single-state model in which receptor-ligand binding equilibria are not influenced by neighboring complexes, clustering of ligand does not enhance total receptor binding. However, if receptor binding energy increases in the presence of neighboring ligated receptors, strong ligand spatial distribution effects arise. Nonlinear responses to increasing ligand density are also observed even in the case of random ligand placement due to stochastic juxtaposition of ligand molecules. These results describe how spatial distribution of ligand presented by the extracellular matrix or by synthetic biomimetic materials might control cell responses to external ligands, and suggest a feedback mechanism by which focal contact formation might be initiated.