论文标题

自由扩展T84上皮细胞菌落的集体旋转运动

Collective rotational motion of freely-expanding T84 epithelial cell colonies

论文作者

Ascione, Flora, Caserta, Sergio, Esposito, Speranza, Villella, Valeria Rachela, Maiuri, Luigi, Nejad, Mehrana R., Doostmohammadi, Amin, Yeomans, Julia M., Guido, Stefano

论文摘要

协调的旋转运动是一种有趣但仍然难以捉摸的集体细胞迁移方式,这与病理和形态发生过程有关。关于该主题的大多数研究都是在受关闭的上皮细胞上进行的。在这种情况下,集体旋转的驱动力尚未清楚地阐明,尽管已经推测空间限制可以在触发细胞旋转中起着至关重要的作用。在这里,我们研究了上皮细胞菌落在细胞培养板表面上自由扩展(即没有物理约束)的生长,这种情况在文献中受到了很少的关注。我们发现,在自由生长状态下的细胞簇中自发地发生了协调的细胞旋转,因此这意味着细胞限制对于引起如前所述的集体旋转不是必需的。集体旋转的尺寸和形状取决于:在具有圆形的小细胞簇中发现了高度协调的磁盘状旋转,而在大型不规则的细胞簇中,集体旋转在生长过程中通过合并不同的簇而产生的大型不规则细胞簇被抑制。角运动在相同的方向上持续存在,尽管顺时针和逆时针旋转同样可能在不同的细胞簇之间发生。与角速度相比,径向细胞速度低。在外围的细胞与簇核心的细胞之间观察到了明显的形态差异,与后者相比,前者更加伸长和散布。总体而言,我们的结果提供了第一个定量和系统的证据,即协调的细胞旋转不需要空间限制,并且自由地发生在自由扩展的上皮细胞菌落中。

Coordinated rotational motion is an intriguing, yet still elusive mode of collective cell migration, which is relevant in pathological and morphogenetic processes. Most of the studies on this topic have been carried out on confined epithelial cells. The driver of collective rotation in such conditions has not been clearly elucidated, although it has been speculated that spatial confinement can play an essential role in triggering cell rotation. Here, we study the growth of epithelial cell colonies freely expanding (i.e., with no physical constraints) on the surface of cell culture plates, a case which has received scarce attention in the literature. We find that coordinated cell rotation spontaneously occurs in cell clusters in the free growth regime, thus implying that cell confinement is not necessary to elicit collective rotation as previously suggested. The collective rotation was size and shape dependent: a highly coordinated disk-like rotation was found in small cell clusters with a round shape, while collective rotation was suppressed in large irregular cell clusters generated by merging of different clusters in the course of their growth. The angular motion was persistent in the same direction, although clockwise and anticlockwise rotations were equally likely to occur among different cell clusters. Radial cell velocity was low as compared to the angular velocity. A clear difference in morphology was observed between cells at the periphery and the ones in the core of the clusters, the former being more elongated and spread out as compared to the latter. Overall, our results provide the first quantitative and systematic evidence that coordinated cell rotation does not require a spatial confinement and occurs spontaneously in freely expanding epithelial cell colonies.

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