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The role of single cell mechanical behavior and polarity in driving collective cell migration.
Nature Physics ( IF 17.6 ) Pub Date : 2020-05-04 , DOI: 10.1038/s41567-020-0875-z
Shreyansh Jain 1, 2 , Victoire M L Cachoux 3 , Gautham H N S Narayana 1 , Simon de Beco 1 , Joseph D'Alessandro 1 , Victor Cellerin 1 , Tianchi Chen 2 , Mélina L Heuzé 1 , Philippe Marcq 4 , René-Marc Mège 1 , Alexandre J Kabla 3 , Chwee Teck Lim 2, 5, 6 , Benoit Ladoux 1
Affiliation  

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis, as well as during pathological events such as wound healing and cancer metastasis. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single-cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring-shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genital or follicular cell rotation. Using our system, we demonstrated that cells follow coordinated rotational movements after establishing directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front–rear polarity within each single cell but does not require the maintenance of cell–cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations can arise from single-cell behaviour through a sustained memory of cell polarity.



中文翻译:

单细胞机械行为和极性在驱动集体细胞迁移中的作用。

细胞群的定向迁移在各种生理过程中是必不可少的,例如外胚层、肠上皮更新和形态发生过程中的会聚延伸,以及在伤口愈合和癌症转移等病理事件中。集体细胞迁移导致在多个细胞上出现协调运动。我们目前的理解强调这些运动主要是由通过粘附连接的大规模信号传输驱动的。在这项研究中,我们表明通过建立协调的 lamellipodial 突起,可以由单细胞水平的极性信号触发上皮细胞的集体运动。我们设计了一个简约的模型系统来生成限制在环形模式中的一维上皮序列,这些模式概括了在体外细胞单层和体内生殖器或滤泡细胞旋转中观察到的旋转运动。使用我们的系统,我们证明了在整个单层上建立定向 Rac1 依赖性极性后,细胞遵循协调的旋转运动。我们的实验和数值方法表明,协调迁移的维持需要在每个单个细胞内获得前后极性,但不需要维持细胞 - 细胞连接。综合起来,

更新日期:2020-05-04
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