Moriel Avraham, Livne Ariel, Bouchbinder Eran
Chemical and Biological Physics Department, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Soft Matter. 2022 Sep 28;18(37):7091-7102. doi: 10.1039/d2sm00611a.
The ability of living cells to sense the physical properties of their microenvironment and to respond to dynamic forces acting on them plays a central role in regulating their structure, function and fate. Of particular importance is the cellular sensitivity and response to periodic driving forces in noisy environments, encountered in vital physiological conditions such as heart beating, blood vessel pulsation and breathing. Here, we first test and validate two predictions of a mean-field theory of cellular reorientation under periodic driving, which combines the minimization of cellular anisotropic elastic energy with active remodeling forces. We then extend the mean-field theory to include uncorrelated, additive nonequilibrium fluctuations, and show that the theory quantitatively agrees with the experimentally observed stationary probability distributions of the cell body orientation, under a range of biaxial periodic driving forces. The fluctuations theory allows the extraction of the dimensionless active noise amplitude of various cell types, and consequently their rotational diffusion coefficient. We then focus on intra-cellular nematic order, on orientational fluctuations of actin stress fibers around the cell body orientation, and show experimentally that intra-cellular nematic order increases with both the magnitude of the driving forces and the biaxiality strain ratio. These results are semi-quantitatively explained by applying the same cell body fluctuations theory to orientationally correlated actin stress fiber domains. Finally, an estimate of the energy scale of cellular orientational fluctuations for one cell type is shown to be about six order of magnitude larger than the thermal energy at room temperature. The implications of our findings, which make the quantitative analysis of cell mechanosensitivity more accessible, are discussed.
活细胞感知其微环境物理特性并对作用于它们的动态力作出反应的能力，在调节细胞结构、功能和命运方面起着核心作用。在诸如心跳、血管搏动和呼吸等重要生理条件下遇到的嘈杂环境中，细胞对周期性驱动力的敏感性和反应尤为重要。在这里，我们首先测试并验证了周期性驱动下细胞重新定向的平均场理论的两个预测，该理论将细胞各向异性弹性能量的最小化与主动重塑力相结合。然后，我们将平均场理论扩展到包括不相关的、加性非平衡涨落，并表明该理论在一系列双轴周期性驱动力下，与实验观察到的细胞体取向的稳态概率分布在定量上一致。涨落理论允许提取各种细胞类型的无量纲主动噪声幅度，从而得到它们的旋转扩散系数。然后，我们关注细胞内的向列序，关注肌动蛋白应力纤维围绕细胞体取向的取向涨落，并通过实验表明细胞内的向列序随着驱动力的大小和双轴应变比的增加而增加。通过将相同的细胞体涨落理论应用于取向相关的肌动蛋白应力纤维域，对这些结果进行了半定量解释。最后，对于一种细胞类型，细胞取向涨落的能量尺度估计比室温下的热能大约大六个数量级。我们讨论了研究结果的意义，这些结果使细胞机械敏感性的定量分析更容易实现。
