论文标题

为什么上皮细胞集体朝着行进信号波移动

Why epithelial cells collectively move against a traveling signal wave

论文作者

Fukuyama, Tatsuya, Ebata, Hiroyuki, Yamamoto, Akihisa, Ienaga, Ryo, Kondo, Yohei, Tanaka, Motomu, Kidoaki, Satoru, Aoki, Kazuhiro, Maeda, Yusuke T.

论文摘要

细胞种群对外部刺激的反应在生物机械过程中起着核心作用,例如上皮伤口愈合和发育形态发生。 ERK MAP激酶信号的波形传播已显示出向一个方向引导集体迁移。但是,在波动波下基于连续力学的机制尚不完全了解。为了阐明ERK激酶信号的行进波如何指导集体迁移,我们通过考虑收缩应力和细胞方向的信号依赖性协调来构建上皮细胞单层的机械模型。通过使用光遗传控制的细胞系统研究了所提出的模型,我们发现局部信号激活诱导细胞密度和方向的变化,并随着传播的方向而变化。细胞种群的净运动相对于波浪发生,迁移速度与ERK信号波的速度共振最大。在\ textIt {Inter}伤口愈合过程中进一步验证了所提出的机械模型。

The response of cell populations to external stimuli plays a central role in biological mechanical processes such as epithelial wound healing and developmental morphogenesis. Wave-like propagation of a signal of ERK MAP kinase has been shown to direct collective migration in one direction; however, the mechanism based on continuum mechanics under a traveling wave is not fully understood. To elucidate how the traveling wave of the ERK kinase signal directs collective migration, we constructed the mechanical model of the epithelial cell monolayer by considering the signal-dependent coordination of contractile stress and cellular orientation. The proposed model was studied by using an optogenetically-controlled cell system where we found that local signal activation induces changes in cell density and orientation with the direction of propagation. The net motion of the cell population occurred relative to the wave, and the migration velocity showed a maximum in resonance with the velocity of the ERK signal wave. The presented mechanical model was further validated in \textit{in vitro} wound healing process.

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