Spontaneous Spatial Correlation of Elastic Modulus in Jammed Epithelial Monolayers Observed by AFM
Spontaneous Spatial Correlation of Elastic Modulus in Jammed Epithelial Monolayers Observed by AFM
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DOI：
10.1016/j.bpj.2019.01.037
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发表时间：
2019-03-19
影响因子：
3.4
通讯作者：
Okajima, Takaharu
中科院分区：
文献类型：
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作者：
Fujii, Yuki;Ochi, Yuki;Okajima, Takaharu
对于衬底上的孤立单细胞，细胞内刚度，通常用原子力显微镜（AFM）测量为杨氏模量E，取决于衬底刚度。然而，在细胞群体系统中，当细胞与相邻细胞物理上紧密接触时，细胞的E是如何受到周围细胞的影响的，我们所知甚少。在这项研究中，我们研究了E在细胞迁移受到高度抑制的堵塞上皮单层中的空间异质性，使我们能够通过AFM精确测量E在大范围区域的空间分布。原子力显微镜测量表明，E可以用两个空间相关长度来表征：较短的相关长度l(S)在单个细胞大小范围内，较长的相关长度l(l)大于相邻细胞之间的距离，对应于e的细胞间相关。我们发现，当化学处理破坏肌动蛋白丝或螯合钙离子时，l(l)显著下降，在冲洗后，减少的l(l)恢复到对照条件下的值。此外，我们发现当E-cadherin被敲低时，l(l)显著降低。这些结果表明，观察到的E的远程相关性并不是固定在堵塞状态下的，而是固有地来自于通过E-钙粘蛋白依赖的细胞-细胞连接形成的大规模肌动蛋白丝结构。
For isolated single cells on a substrate, the intracellular stiffness, which is often measured as the Young's modulus, E, by atomic force microscopy (AFM), depends on the substrate rigidity. However, little is known about how the E of cells is influenced by the surrounding cells in a cell population system in which cells physically and tightly contact adjacent cells. In this study, we investigated the spatial heterogeneities of E in a jammed epithelial monolayer in which cell migration was highly inhibited, allowing us to precisely measure the spatial distribution of E in large-scale regions by AFM. The AFM measurements showed that E can be characterized using two spatial correlation lengths: the shorter correlation length, l(S), is within the single cell size, whereas the longer correlation length, l(L), is longer than the distance between adjacent cells and corresponds to the intercellular correlation of E. We found that l(L) decreased significantly when the actin filaments were disrupted or calcium ions were chelated using chemical treatments, and the decreased l(L) recovered to the value in the control condition after the treatments were washed out. Moreover, we found that l(L) decreased significantly when E-cadherin was knocked down. These results indicate that the observed long-range correlation of E is not fixed within the jammed state but inherently arises from the formation of a large-scale actin filament structure via E-cadherin-dependent cell-cell junctions.