Cell tension and mechanical regulation of cell volume.
Cell tension and mechanical regulation of cell volume.
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DOI：
10.1091/mbc.e18-04-0213
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发表时间：
2018-10-15
影响因子：
3.3
通讯作者：
Sun SX
中科院分区：
文献类型：
--
作者：
Perez Gonzalez N;Tao J;Rochman ND;Vig D;Chiu E;Wirtz D;Sun SX
动物细胞使用一种未知的机制来控制它们的生长和物理大小。在这里，使用荧光排除法，我们测量细胞体积的不同刚度的基板上的贴壁细胞。我们发现，细胞体积有一个复杂的依赖于基板的刚度和正相关的细胞粘附到基板的大小。从一个机械力平衡条件，决定了细胞表面的几何形状，我们发现，所观察到的细胞体积的变化可以定量预测通过细胞皮质的活性肌球蛋白的分布。为了将细胞机械张力与细胞大小的稳态联系起来，我们定量了雅普/TAZ（一种参与细胞生长和增殖的转录因子）的核定位。我们发现细胞核雅普/TAZ的水平与细胞平均体积呈正相关。此外，核雅普/TAZ的水平也与细胞张力有关，如通过磷酸化肌球蛋白的量所测量的。具有更大顶端张力的细胞倾向于具有更高水平的核雅普/TAZ和更大的细胞体积。这些结果指出了基于机械张力的尺寸传感机制：细胞张力随着细胞生长而增加，并且增加的张力以生物化学方式反馈到生长和增殖控制。
Animal cells use an unknown mechanism to control their growth and physical size. Here, using the fluorescence exclusion method, we measure cell volume for adherent cells on substrates of varying stiffness. We discover that the cell volume has a complex dependence on substrate stiffness and is positively correlated with the size of the cell adhesion to the substrate. From a mechanical force–balance condition that determines the geometry of the cell surface, we find that the observed cell volume variation can be predicted quantitatively from the distribution of active myosin through the cell cortex. To connect cell mechanical tension with cell size homeostasis, we quantified the nuclear localization of YAP/TAZ, a transcription factor involved in cell growth and proliferation. We find that the level of nuclear YAP/TAZ is positively correlated with the average cell volume. Moreover, the level of nuclear YAP/TAZ is also connected to cell tension, as measured by the amount of phosphorylated myosin. Cells with greater apical tension tend to have higher levels of nuclear YAP/TAZ and a larger cell volume. These results point to a size-sensing mechanism based on mechanical tension: the cell tension increases as the cell grows, and increasing tension feeds back biochemically to growth and proliferation control.