Formation of adherens junctions leads to the emergence of a tissue-level tension in epithelial monolayers.

Formation of adherens junctions leads to the emergence of a tissue-level tension in epithelial monolayers.
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DOI:
10.1242/jcs.142349
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发表时间:
2014-06-01
影响因子:
4
通讯作者:
Charras GT
Charras GT
中科院分区:
生物学2区
文献类型:
--
作者:
Harris AR;Daeden A;Charras GT

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粘附连接和桥粒将相邻细胞的细胞骨架整合成一个机械合胞。在这样做的过程中,细胞间连接赋予组织承受正常生理中遇到的机械应力所需的强度,并在形态发生期间协调张力。虽然对结形成的生物学机制了解很多,但对如何建立组织尺度的力学特性知之甚少。在这里,我们使用深原子力显微镜(AFM)压痕来测量从游离细胞重组的上皮单层的表观刚度,并检查哪些细胞过程引起组织尺度力学。我们表明,细胞间连接的形成与重组单层表观刚度的增加相一致,这反映了组织水平张力的产生。张力迅速增加,在150分钟后达到最大值,然后在接下来的3小时内稳定到较低的水平,因为单层膜建立了稳态。组织张力的出现与粘附连接的形成有关,而与桥粒的形成无关。因此,任何参与粘附连接起始、重塑和成熟的分子机制的抑制都显著阻碍了单分子膜中组织水平张力的出现。
Adherens junctions and desmosomes integrate the cytoskeletons of adjacent cells into a mechanical syncitium. In doing so, intercellular junctions endow tissues with the strength needed to withstand the mechanical stresses encountered in normal physiology and to coordinate tension during morphogenesis. Though much is known about the biological mechanisms underlying junction formation, little is known about how tissue-scale mechanical properties are established. Here, we use deep atomic force microscopy (AFM) indentation to measure the apparent stiffness of epithelial monolayers reforming from dissociated cells and examine which cellular processes give rise to tissue-scale mechanics. We show that the formation of intercellular junctions coincided with an increase in the apparent stiffness of reforming monolayers that reflected the generation of a tissue-level tension. Tension rapidly increased, reaching a maximum after 150 min, before settling to a lower level over the next 3 h as monolayers established homeostasis. The emergence of tissue tension correlated with the formation of adherens junctions but not desmosomes. As a consequence, inhibition of any of the molecular mechanisms participating in adherens junction initiation, remodelling and maturation significantly impeded the emergence of tissue-level tension in monolayers.
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