Mechanical Stress Inference for Two Dimensional Cell Arrays
Mechanical Stress Inference for Two Dimensional Cell Arrays
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DOI：
10.1371/journal.pcbi.1002512
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发表时间：
2012-05-01
影响因子：
4.3
通讯作者：
Shraiman, Boris I.
中科院分区：
文献类型：
--
作者：
Chiou, Kevin K.;Hufnagel, Lars;Shraiman, Boris I.
许多形态发生过程涉及上皮组织的机械重排，其由精确调节的细胞骨架力和细胞粘附驱动。细胞的机械状态和细胞间粘附不仅是调控的目标，而且本身也是协调发育过程的可能信号。然而，由于很难在亚细胞尺度上直接测量体内的机械应力，因此对力学在发育中的作用知之甚少。在这里，我们提出了一种替代方法，利用最近的进展，在现场成像的形态发生过程，并使用计算分析的高分辨率图像的上皮组织，以推断细胞内和细胞之间的相对大小的力量。我们模拟细胞内的压力和界面张力，允许这些参数从细胞到细胞，从接口到接口。假设上皮细胞层接近机械平衡，我们使用观察到的二维细胞阵列的几何形状来推断界面张力和细胞内压力。在这里，我们提出了建议的机械逆方法的数学公式，并将其应用于分析观察到的腹沟形成在果蝇胚胎的发病时的上皮细胞层，并在禽耳蜗毛细胞测定的过程中。分析表明，在前一个过程中的机械各向异性和机械的异质性，与细胞分化，在后一个过程中。该方法为细胞和组织力学模型的定量和详细的实验测试开辟了一条道路。
Many morphogenetic processes involve mechanical rearrangements of epithelial tissues that are driven by precisely regulated cytoskeletal forces and cell adhesion. The mechanical state of the cell and intercellular adhesion are not only the targets of regulation, but are themselves the likely signals that coordinate developmental process. Yet, because it is difficult to directly measure mechanical stress in vivo on sub-cellular scale, little is understood about the role of mechanics in development. Here we present an alternative approach which takes advantage of the recent progress in live imaging of morphogenetic processes and uses computational analysis of high resolution images of epithelial tissues to infer relative magnitude of forces acting within and between cells. We model intracellular stress in terms of bulk pressure and interfacial tension, allowing these parameters to vary from cell to cell and from interface to interface. Assuming that epithelial cell layers are close to mechanical equilibrium, we use the observed geometry of the two dimensional cell array to infer interfacial tensions and intracellular pressures. Here we present the mathematical formulation of the proposed Mechanical Inverse method and apply it to the analysis of epithelial cell layers observed at the onset of ventral furrow formation in the Drosophila embryo and in the process of hair-cell determination in the avian cochlea. The analysis reveals mechanical anisotropy in the former process and mechanical heterogeneity, correlated with cell differentiation, in the latter process. The proposed method opens a way for quantitative and detailed experimental tests of models of cell and tissue mechanics.