E-cadherin-dependent coordinated epithelial rotation on a two-dimensional discoidal pattern
E-cadherin-dependent coordinated epithelial rotation on a two-dimensional discoidal pattern
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DOI：
10.1111/gtc.13001
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发表时间：
2022-12-30
期刊：
影响因子：
2.1
通讯作者：
Uemura, Tadashi
中科院分区：
文献类型：
--
作者：
Luo, Shuangyu;Furuya, Kanji;Uemura, Tadashi
在体内，细胞在各种发育和病理背景下集体迁移。协调的上皮旋转代表了一种独特的集体细胞迁移类型，已在空间受限条件下进行了体外建模。尽管众所周知，协调旋转取决于细胞间相互作用，但 E-钙粘蛋白（一种主要的细胞间粘附分子）的贡献尚未在二维 (2D) 受限基质上直接得到解决。在这里，我们使用控制良好的纤连蛋白涂层表面，跟踪并比较了表达或缺乏 E-钙粘蛋白的 MDCK 细胞的迁移行为。我们观察到野生型 MDCK II 细胞在盘状模式上表现出持续且协调的旋转，而 E-钙粘蛋白敲除细胞以不太协调的方式迁移，没有大规模旋转。我们对这两种细胞类型之间的集体动力学的比较揭示了由 E-钙粘蛋白的丢失引起的一系列迁移行为的变化，包括整体迁移速度降低、量化协调的规律性降低以及拓扑缺陷的平均密度增加。总而言之，这些数据表明集体上皮旋转的自发启动取决于 2D 盘状限制下的 E-钙粘蛋白。
In vivo, cells collectively migrate in a variety of developmental and pathological contexts. Coordinated epithelial rotation represents a unique type of collective cell migrations, which has been modeled in vitro under spatially confined conditions. Although it is known that the coordinated rotation depends on intercellular interactions, the contribution of E-cadherin, a major cell-cell adhesion molecule, has not been directly addressed on two-dimensional (2D) confined substrates. Here, using well-controlled fibronectin-coated surfaces, we tracked and compared the migratory behaviors of MDCK cells expressing or lacking E-cadherin. We observed that wild-type MDCK II cells exhibited persistent and coordinated rotations on discoidal patterns, while E-cadherin knockout cells migrated in a less coordinated manner without large-scale rotation. Our comparison of the collective dynamics between these two cell types revealed a series of changes in migratory behavior caused by the loss of E-cadherin, including a decreased global migration speed, less regularity in quantified coordination, and increased average density of topological defects. Taken together, these data demonstrate that spontaneous initiation of collective epithelial rotations depends on E-cadherin under 2D discoidal confinements.