Integrin dimerization and ligand organization: Key components in integrin clustering for cell adhesion
Integrin dimerization and ligand organization: Key components in integrin clustering for cell adhesion
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DOI：
10.1089/ten.2005.11.865
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发表时间：
2005-05-01
影响因子：
--
通讯作者：
Linderman, JJ
中科院分区：
文献类型：
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作者：
Brinkerhoff, CJ;Linderman, JJ
细胞粘附需要整合素占据和整合素聚集。在这项工作中，我们调查的基础上组织配体成岛和整合素二聚化的整合素集群的启动机制。为了研究整联蛋白的聚集和整联蛋白的占据，我们开发了一个二维的Monte Carlo晶格描述的细胞-基底界面来模拟整联蛋白的扩散和反应。我们证明，整合素二聚化可以驱动整合素成簇的大小大于两个。单独的配体组织或整联蛋白二聚化无法增加结合的整联蛋白的数量，但当两者都存在时，它们相互合作以增加整联蛋白的结合和聚集。此外，当整联蛋白二聚化和配体组织都存在时，观察到大的整联蛋白簇，其可以作为形成粘附复合物的成核位点。这些结果描述了一个潜在的机制，在细胞粘附的整合素受体和亲合力调制的集群，并有影响的表面设计，以控制细胞对外部配体的反应，并操纵细胞粘附的组织工程应用。
Cell adhesion requires both integrin occupancy and integrin clustering. In this work, we investigate a mechanism based on organizing ligand into islands and integrin dimerization for the initiation of integrin clustering. To study integrin clustering and integrin occupancy we develop a two-dimensional Monte Carlo lattice description of the cell-substrate interface to simulate the diffusion and reaction of integrins. We demonstrate that integrin dimerization can drive integrins into clusters of sizes greater than two. Ligand organization or integrin dimerization alone is unable to increase the number of bound integrins, but when both are present they cooperate to increase both binding and clustering of integrins. In addition, when integrin dimerization and ligand organization are both present large integrin clusters, which may act as nucleation sites for the formation of adhesion complexes, are observed. These results describe a potential mechanism for the clustering of integrin receptors and avidity modulation in cellular adhesion and have implications for the designs of surfaces to control cell responses to external ligands and to manipulate cell adhesion for tissue-engineering applications.