上皮细胞为何集体逆着行进信号波移动
Why epithelial cells collectively move against a traveling signal wave
AI总结:
本文构建了考虑信号依赖收缩应力与细胞取向的上皮单层力学模型,结合光遗传学实验揭示ERK信号行进波通过共振机制引导集体迁移,并在体外伤口愈合中验证了模型。
摘要:
细胞群体对外部刺激的响应在上皮伤口愈合和发育形态发生等生物力学过程中起着核心作用。ERK MAP激酶信号的波状传播已被证明能够引导集体迁移沿单一方向进行;然而,基于连续介质力学在行进波作用下的机制尚未被充分理解。为了阐明ERK激酶信号的行进波如何引导集体迁移,我们通过考虑信号依赖的收缩应力协调和细胞取向,构建了上皮细胞单层的力学模型。利用光遗传学控制的细胞系统对所提出的模型进行了研究,我们发现局部信号激活会诱导细胞密度和取向沿传播方向发生变化。细胞群体的净运动相对于波发生,并且迁移速度在与ERK信号波速度共振时呈现最大值。所提出的力学模型进一步在体外伤口愈合过程中得到了验证。
英文摘要:
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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