Tight junctions control lumen morphology via hydrostatic pressure and junctional tension

IF 10.7 1区 生物学 Q1 CELL BIOLOGY Developmental cell Pub Date : 2024-08-12 DOI:10.1016/j.devcel.2024.07.016
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Abstract

Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for the hydraulic inflation of a lumen. However, the depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements of hydrostatic lumen pressure and junctional tension with modeling enabled us to explain lumen morphologies from the pressure-tension force balance. Tight junctions promote lumen inflation by decreasing cortical tension via the inhibition of myosin. In addition, our results suggest that excess apical area contributes to lumen opening. Overall, we provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape.

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紧密连接通过静水压力和连接张力控制管腔形态
上皮组织形成充满液体的管腔对器官发育至关重要。细胞如何控制水力和皮质力来控制管腔形态还不十分清楚。在这里,我们利用 MDCK-II 囊肿量化了紧密连接在管腔形成中的机械作用。我们发现,管腔的水力膨胀并不需要由 claudin 受体形成的细胞旁离子屏障。然而,封闭带支架的耗竭会导致管腔塌陷和顶端膜折叠。将腔内静水压和连接张力的定量测量与建模相结合,使我们能够从压力-张力平衡中解释腔内形态。紧密连接通过抑制肌球蛋白降低皮质张力,从而促进管腔膨胀。此外,我们的研究结果表明,过大的顶端面积有助于管腔开放。总之,我们从力学角度理解了上皮细胞如何利用紧密连接来调节组织和管腔形状。
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来源期刊
Developmental cell
Developmental cell 生物-发育生物学
CiteScore
18.90
自引率
1.70%
发文量
203
审稿时长
3-6 weeks
期刊介绍: Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.
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