Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role in regulating cell cohesion and migration dynamics during tissue remodeling. While the role and origin of the junctional mechanical tension at AJs have been extensively studied, the influence of the actin cortex structure and dynamics on junction plasticity remains incompletely understood. Moreover, the mechanisms underlying stress dissipation at junctions are not well elucidated. Here, we found that the ligand-independent phosphorylation of epithelial growth factor receptor (EGFR) downstream of de novo E-cadherin adhesion orchestrates a feedback loop, governing intercellular viscosity via the Rac pathway regulating actin dynamics. Our findings highlight how the E-cadherin-dependent EGFR activity controls the migration mode of collective cell movements independently of intercellular tension. This modulation of effective viscosity coordinates cellular movements within the expanding monolayer, inducing a transition from swirling to laminar flow patterns while maintaining a constant migration front speed. Additionally, we propose a vertex model with adjustable junctional viscosity, capable of replicating all observed cellular flow phenotypes experimentally.

中文翻译：

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EGFR 的 E-钙粘蛋白依赖性磷酸化在细胞集体迁移中对细胞间粘度的调节


细胞集体迁移在各种生理过程中至关重要，包括伤口愈合、形态发生和癌症转移。粘附连接 （AJ） 在组织重塑过程中调节细胞内聚和迁移动力学中起着关键作用。虽然 AJ 连接机械张力的作用和起源已被广泛研究，但肌动蛋白皮层结构和动力学对连接可塑性的影响仍不完全清楚。此外，结处应力耗散的潜在机制尚未得到很好的阐明。在这里，我们发现从头 E-钙粘蛋白粘附下游的上皮生长因子受体 （EGFR） 的配体非依赖性磷酸化协调了一个反馈回路，通过调节肌动蛋白动力学的 Rac 途径控制细胞间粘度。我们的研究结果强调了 E-钙粘蛋白依赖性 EGFR 活性如何独立于细胞间张力控制集体细胞运动的迁移模式。这种有效粘度的调节协调膨胀的单层内的细胞运动，诱导从漩涡流模式过渡到层流模式，同时保持恒定的迁移前沿速度。此外，我们提出了一种具有可调节连接粘度的顶点模型，能够通过实验复制所有观察到的细胞流动表型。