Src 激酶减缓封闭上皮细胞单层的集体旋转

Nastassia Pricoupenko, Flavia Marsigliesi, Philippe Marcq, Carles Blanch-Mercader, Isabelle Bonnet
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摘要

细胞集体迁移是发育、伤口愈合和转移过程中的关键,依赖于细胞在群体水平上的协调行为。Srckinase是一种信号酶,可调控许多细胞过程,包括粘附和运动,它的失调激活与不同癌症的侵袭性有关。在这里,我们利用光遗传学的优势,及时精确地控制 Src 的激活,研究其过度激活对封闭单层细胞集体旋转的影响。我们的研究表明,Src 激活会减缓封闭在环形粘附斑块中的上皮细胞的集体旋转。我们通过将细胞集结为极性活性流体的流体力学描述来解释 Src 未激活和激活期间的速度、力和应力数据。Src 激活导致极角与摩擦力之比下降了 2 倍,这可能是由于细胞与基底界面的粘合键增加所致。我们的研究揭示了微调 Src 活性水平对协调集体行为的重要性。
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Src Kinase Slows Collective Rotation of Confined Epithelial Cell Monolayers
Collective cell migration is key during development, wound healing and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a signalling enzyme regulating many cellular processes including adhesion and motility and its deregulated activation has been associated to aggressiveness of different cancers. Here, we take advantage of optogenetics to precisely control Src activation in time to study the effect of its over activation on collective rotation of confined monolayers. We show that Src activation slows down collective rotation of epithelial cells confined into circular adhesive patches. We interpret velocity, force and stress data during period of non-activation and period of activation of Src thanks to an hydrodynamic description of the cell assembly as a polar active fluid. Src activation leads to a 2-fold decrease in the ratio of polar angle to friction, which could result from increased adhesive bonds at the cell-substrate interface. Our work reveals the importance of fine-tuning the level of Src activity for coordinated collective behaviors.
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