Cell migration through defined, synthetic extracellular matrix analogues
Cell migration through defined, synthetic extracellular matrix analogues
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DOI：
10.1096/fj.01-0759fje
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发表时间：
2002-03-01
期刊：
影响因子：
4.8
通讯作者：
West, JL
中科院分区：
文献类型：
--
作者：
Gobin, AS;West, JL
我们已经开发了合成的水凝胶细胞外基质（ECM）类似物，可用于研究细胞迁移的机制，如受体-配体相互作用和蛋白质水解。该仿生水凝胶由生物惰性聚乙二醇二丙烯酸酯衍生物组成，其蛋白水解可降解肽序列包含在聚合物的主链中，并接枝到网络上的粘附肽序列。水凝胶已经被开发出来，可以随着细胞分泌蛋白水解酶而降解。接枝到水凝胶上的粘附肽序列提供了可以与细胞表面受体相互作用的配体，以介导粘附和扩散。在这项研究中，我们描述了黏附配体密度对成纤维细胞通过胶原酶可降解和纤溶酶可降解水凝胶迁移以及对平滑肌细胞通过弹性酶可降解水凝胶迁移的影响。在这三种情况下，我们发现细胞迁移对粘附配体浓度有双相依赖性，在中等配体水平时迁移最佳。此外，粘附和蛋白降解序列都是细胞迁移发生所必需的。这些合成的ECM类似物可能对细胞迁移的许多方面的三维机制研究有用。
We have developed synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable and plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogues may be useful for 3-D mechanistic studies of many aspects of cell migration.