Substrate engagement of integrins α5β1 and αvβ3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin
Substrate engagement of integrins α5β1 and αvβ3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin
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DOI：
10.1038/srep23258
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发表时间：
2016-03-18
影响因子：
4.6
通讯作者：
Spatz, Joachim P.
中科院分区：
文献类型：
--
作者：
Missirlis, Dimitris;Haraszti, Tamas;Spatz, Joachim P.
特异性整合素介导的基质粘附和细胞迁移中的定向持久性之间的相互作用还不清楚。在这里，我们的特点是成纤维细胞的粘附和迁移的细胞外基质糖蛋白纤连蛋白和玻连蛋白，集中在α（5）β（1）和α（V）β（3）整合素的作用。成纤维细胞表现出高定向持久性迁移纤连蛋白，但不是玻连蛋白包被的基板上，在配体密度依赖性的方式。纤连蛋白刺激肌动蛋白细胞骨架的α（5）β（1）依赖性组织形成定向的腹侧应力纤维，以及动态极化突起的组装，其特征在于没有应力纤维的区域，并且在其边缘处富含新生粘附。这种突起与持续的局部前缘前移相关，但对于较长时间的定向迁移来说并不充分，也不是必需的。使用小分子整联蛋白拮抗剂选择性阻断α（v）β（3）或α（5）β（1）整联蛋白降低了在纤连蛋白上的方向持久性，表明整联蛋白在维持方向性方面的协同性。另一方面，设计成选择性接合整联蛋白或其组合的图案化基底不足以建立定向迁移。总的来说，我们的研究证明了成纤维细胞迁移中定向持久性的粘附涂层依赖性调节，并挑战了先前提出的β（1）和β（3）整合素在定向迁移中作用的普遍性。
The interplay between specific integrin-mediated matrix adhesion and directional persistence in cell migration is not well understood. Here, we characterized fibroblast adhesion and migration on the extracellular matrix glycoproteins fibronectin and vitronectin, focusing on the role of alpha(5)beta(1) and alpha(v)beta(3) integrins. Fibroblasts manifested high directional persistence in migration on fibronectin-, but not vitronectin-coated substrates, in a ligand density-dependent manner. Fibronectin stimulated alpha(5)beta(1)-dependent organization of the actin cytoskeleton into oriented, ventral stress fibers, and assembly of dynamic, polarized protrusions, characterized as regions free of stress fibers and rich in nascent adhesions at their edge. Such protrusions correlated with persistent, local leading edge advancement, but were not sufficient, nor necessary for directional migration over longer times. Selective blocking of alpha(v)beta(3) or alpha(5)beta(1) integrins using small molecule integrin antagonists reduced directional persistence on fibronectin, indicating integrin cooperativity in maintaining directionality. On the other hand, patterned substrates, designed to selectively engage either integrin, or their combination, were not sufficient to establish directional migration. Overall, our study demonstrates adhesive coating-dependent regulation of directional persistence in fibroblast migration and challenges the generality of the previously suggested role of beta(1) and beta(3) integrins in directional migration.