Src kinase slows collective rotation of confined epithelial cell monolayers†

IF 2.9 3区 化学 Q3 CHEMISTRY, PHYSICAL
Soft Matter Pub Date : 2024-11-01 DOI:10.1039/D4SM00827H
Nastassia Pricoupenko, Flavia Marsigliesi, Philippe Marcq, Carles Blanch-Mercader and Isabelle Bonnet
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引用次数: 0

Abstract

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 key signalling protein for the physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its overactivation is associated with cancer aggressiveness. Here, we take advantage of optogenetics to precisely control Src activation in time and show that its pathological-like activation slows the 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 a 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 adhesiveness at the cell–substrate interface. Measuring internal stress allows us to show that active stresses are subdominant compared to traction forces. Our work reveals the importance of fine-tuning the level of Src activity for coordinated collective behaviors.

Abstract Image

Src激酶可减缓封闭上皮细胞单层的集体旋转。
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。Src 激酶是上皮细胞生理功能的关键信号蛋白,因为它调控许多细胞过程,包括粘附、运动和机械传导。它的过度激活与癌症的侵袭性有关。在这里,我们利用光遗传学来精确控制 Src 的及时激活,并证明其病理样激活会减慢局限于圆形粘附斑块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的比率下降了 2 倍,这可能是由于细胞与基底界面的粘附力增加所致。通过测量内应力,我们可以发现与牵引力相比,主动应力处于次要地位。我们的工作揭示了微调 Src 活性水平对于协调集体行为的重要性。
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来源期刊
Soft Matter
Soft Matter 工程技术-材料科学:综合
CiteScore
6.00
自引率
5.90%
发文量
891
审稿时长
1.9 months
期刊介绍: Soft Matter is an international journal published by the Royal Society of Chemistry using Engineering-Materials Science: A Synthesis as its research focus. It publishes original research articles, review articles, and synthesis articles related to this field, reporting the latest discoveries in the relevant theoretical, practical, and applied disciplines in a timely manner, and aims to promote the rapid exchange of scientific information in this subject area. The journal is an open access journal. The journal is an open access journal and has not been placed on the alert list in the last three years.
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