Mukenhirn Markus, Wang Chen-Ho, Guyomar Tristan, Bovyn Matthew J, Staddon Michael F, van der Veen Rozemarijn E, Maraspini Riccardo, Lu Linjie, Martin-Lemaitre Cecilie, Sano Masaki, Lehmann Martin, Hiraiwa Tetsuya, Riveline Daniel, Honigmann Alf
Biotechnology Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01069 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01309 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, 01309 Dresden, Germany.
Dev Cell. 2024 Nov 4;59(21):2866-2881.e8. doi: 10.1016/j.devcel.2024.07.016. Epub 2024 Aug 12.
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.
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以控制管腔形态尚不清楚。在这里，我们使用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，由claudin受体形成的细胞旁离子屏障对于管腔的水力膨胀不是必需的。然而，紧密连接支架的缺失导致管腔塌陷和顶端膜折叠。将静水腔压力和连接张力的定量测量与建模相结合，使我们能够从压力-张力平衡来解释管腔形态。紧密连接通过抑制肌球蛋白降低皮质张力来促进管腔膨胀。此外，我们的结果表明，过多的顶端面积有助于管腔开放。总体而言，我们对上皮细胞如何利用紧密连接来调节组织和管腔形状提供了机械学理解。
