Substrates for Mechanistic Studies of Cell Adhesion

描述：(申请者描述)本研究项目将研究哺乳动物黏附和迁移的分子相互作用 蛋白质细胞外基质上的细胞。适当的配体-受体相互作用 是在发育和发育中引导组织结构形成所必需的 也是为了保持组织的完整性。失去适当的互动 细胞和蛋白质基质之间在癌症和许多其他疾病中起着作用 疾病。本研究将开发一类基于以下因素的模型基板 可完全控制的硫代烷基硫酸盐在金表面的自组装单分子膜 细胞表面受体与之相互作用的固定化配体。这些 底物将用于表征细胞外基质的配体。 它们对粘附性很重要，并将研究 细胞对这些配体有反应。这项研究将针对三个方面 目标。呈现Arg-Gly-Asp多肽和相关类似物的底物将是 用于研究整合素受体动态过程的重要性 细胞黏附和迁移中的相互作用。第二个主题将使用单层 目的：探讨孤儿配体引导细胞附着的机制。一个 第三项工作将使用呈现数百种多肽的底物来 确定对黏附和迁移具有重要作用的新配体。

DESCRIPTION: (Applicant's Description) This research program will investigate the molecular interactions underlying the adhesion and migration of mammalian cells on the protein extracellular matrix. Proper ligand-receptor interactions are required for guiding the formation of tissue structure in development and also for maintaining the integrity of tissue. The loss of proper interactions between cells and the protein matrix plays a role in cancer and in many other diseases. This research will develop a class of model substrates based on self-assembled monolayers of alkanethiolates on gold that can control entirely the immobilized ligands with which cell surface receptors interact. These substrates will be used to characterize ligands of the extracellular matrix that are important in adhesion and will investigate the mechanisms by which cells respond to these ligands. The research will be directed towards three goals. Substrates presenting Arg-Gly-Asp peptides and related analogs will be used to investigate the importance of dynamic processes of integrin-receptor interactions in cell adhesion and migration. A second theme will use monolayers to investigate the mechanisms by which orphan ligands direct cell attachment. A third effort will use substrates presenting an array of hundreds of peptides to identify new ligands that are important in adhesion and migration.