Polarized interfacial tension induces collective migration of cells, as a cluster, in a 3D tissue
Polarized interfacial tension induces collective migration of cells, as a cluster, in a 3D tissue
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极化界面张力诱导 3D 组织中细胞作为簇的集体迁移
DOI：
10.1016/j.bpj.2022.04.018
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发表时间：
2022
影响因子：
3.4
通讯作者：
Sato Katsuhiko
中科院分区：
文献类型：
--
作者：
Okuda Satoru;Sato Katsuhiko
在胚胎发生和癌症侵袭中，细胞在3D组织中集体迁移为一个簇。许多研究已经阐明了单个或集体细胞在2D基质上迁移的机制;然而，目前尚不清楚细胞如何集体迁移作为一个集群通过3D组织。为了解决这个问题，我们认为在细胞-细胞边界的界面张力表达皮质肌动球蛋白收缩和细胞-细胞粘附相互作用。这种张力的强度是两极化的;即，根据化学引诱物梯度在每个细胞内空间偏向。使用三维顶点模型，我们进行了三维空间中的多细胞动力学的数值模拟。模拟显示，极化的界面张力使细胞能够作为一个簇集体迁移通过3D组织。在这种机制中，界面张力诱导每个细胞表面沿着簇表面从前到后沿着单向流动。重要的是，这种机制不一定需要细胞的对流，即，细胞重排，在集群内。此外，诱导了几种迁移模式，这取决于极性、粘附和噪声的强度;即，细胞以单个细胞、成簇或像串珠一样排列的形式迁移，如胚胎发生和癌症侵袭中所发生的。这些结果表明，细胞-细胞边界的简单扩张和收缩使细胞能够定向向前移动，并产生在生命系统中观察到的各种集体迁移运动。
In embryogenesis and cancer invasion, cells collectively migrate as a cluster in 3D tissues. Many studies have elucidated mechanisms of either individual or collective cell migration on 2D substrates; however, it remains unclear how cells collectively migrate as a cluster through 3D tissues. To address this issue, we considered the interfacial tension at cell-cell boundaries expressing cortical actomyosin contractions and cell-cell adhesive interactions. The strength of this tension is polarized; i.e., spatially biased within each cell according to a chemoattractant gradient. Using a 3D vertex model, we performed numerical simulations of multicellular dynamics in 3D space. The simulations revealed that the polarized interfacial tension enables cells to migrate collectively as a cluster through a 3D tissue. In this mechanism, interfacial tension induces unidirectional flow of each cell surface from the front to the rear along the cluster surface. Importantly, this mechanism does not necessarily require convection of cells, i.e., cell rearrangement, within the cluster. Moreover, several migratory modes were induced, depending on the strengths of polarity, adhesion, and noise; i.e., cells migrate either as single cells, as a cluster, or aligned like beads on a string, as occurs in embryogenesis and cancer invasion. These results indicate that the simple expansion and contraction of cell-cell boundaries enables cells to move directionally forward and to produce the variety of collective migratory movements observed in living systems.