Migratory cells are known to adapt to environments that contain wide-ranging levels of chemoattractant. Although biochemical models of adaptation have been previously proposed, here, we discuss a different mechanism based on mechanosensing, in which the interaction between biochemical signaling and cell tension facilitates adaptation. We describe and analyze a model of mechanochemical-based adaptation coupling a mechanics-based physical model of cell tension coupled with the wave-pinning reaction-diffusion model for Rac GTPase activity. The mathematical analysis of this model, simulations of a simplified one-dimensional cell geometry, and two-dimensional finite element simulations of deforming cells reveal that as a cell protrudes under the influence of high stimulation levels, tension-mediated inhibition of Rac signaling causes the cell to polarize even when initially overstimulated. Specifically, tension-mediated inhibition of Rac activation, which has been experimentally observed in recent years, facilitates this adaptation by countering the high levels of environmental stimulation. These results demonstrate how tension-related mechanosensing may provide an alternative (and potentially complementary) mechanism for cell adaptation.

中文翻译：

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膜张力可以增强适应以维持迁移细胞的极性


众所周知，迁移细胞能够适应含有多种化学引诱剂的环境。尽管之前已经提出了适应的生化模型，但在这里，我们讨论了基于机械传感的不同机制，其中生化信号和细胞张力之间的相互作用促进了适应。我们描述并分析了基于机械化学的适应模型，该模型将基于力学的细胞张力物理模型与 Rac GTP 酶活性的波钉扎反应扩散模型相结合。该模型的数学分析、简化的一维细胞几何形状的模拟以及变形细胞的二维有限元模拟表明，当细胞在高刺激水平的影响下突出时，张力介导的 Rac 信号传导抑制会导致即使最初受到过度刺激，细胞也会极化。具体来说，近年来通过实验观察到的张力介导的 Rac 激活抑制通过对抗高水平的环境刺激来促进这种适应。这些结果证明了与张力相关的机械传感如何为细胞适应提供替代（且可能互补）的机制。