Vertical uniformity of cells and nuclei in epithelial monolayers

Vertical uniformity of cells and nuclei in epithelial monolayers
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DOI:
10.1038/srep19689
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发表时间:
2016-01-22
期刊:
影响因子:
4.6
通讯作者:
Lele, Tanmay P.
Lele, Tanmay P.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Neelam, Srujana;Hayes, Peter Robert;Lele, Tanmay P.

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细胞骨架组织、细胞器位置和细胞边界的形态变异是培养细胞的共同特征。通过给细胞提供确定的几何线索,可以实现结构的显著均匀性和再现性。组织中的细胞也可以在没有直接细胞外信号的情况下自组织;然而,这种自组织的机械原理还不清楚。我们报告说,与水平形状,垂直形状的细胞和细胞核在z-维是均匀的细胞培养单层相比,孤立的细胞。单层细胞和细胞核顶面平坦,高度均匀。相反,分离的细胞,或细胞与细胞粘附破坏的细胞具有弯曲的顶面和可变高度的细胞核。在微米大小的方形威尔斯孔中培养的分离细胞显示出与单层细胞相似的扁平细胞和核形状。核-细胞骨架连接的局部破坏导致垂直均匀性的空间变化。这些结果表明,细胞-细胞拉力之间的竞争使垂直细胞横截面扩大和缩短,从而使细胞核变宽和变平,而细胞核对进一步变平的阻力导致均匀的细胞和细胞核横截面。我们的研究结果揭示了细胞单层自组织垂直均匀性的力学原理。
Morphological variability in cytoskeletal organization, organelle position and cell boundaries is a common feature of cultured cells. Remarkable uniformity and reproducibility in structure can be accomplished by providing cells with defined geometric cues. Cells in tissues can also self-organize in the absence of directing extracellular cues; however the mechanical principles for such self-organization are not understood. We report that unlike horizontal shapes, the vertical shapes of the cell and nucleus in the z-dimension are uniform in cells in cultured monolayers compared to isolated cells. Apical surfaces of cells and their nuclei in monolayers were flat and heights were uniform. In contrast, isolated cells, or cells with disrupted cell-cell adhesions had nuclei with curved apical surfaces and variable heights. Isolated cells cultured within micron-sized square wells displayed flat cell and nuclear shapes similar to cells in monolayers. Local disruption of nuclear-cytoskeletal linkages resulted in spatial variation in vertical uniformity. These results suggest that competition between cell-cell pulling forces that expand and shorten the vertical cell cross-section, thereby widening and flattening the nucleus, and the resistance of the nucleus to further flattening results in uniform cell and nuclear cross-sections. Our results reveal the mechanical principles of self-organized vertical uniformity in cell monolayers.