{"title":"Active hole formation in epithelioid tissues","authors":"Jian-Qing Lv, Peng-Cheng Chen, Yun-Ping Chen, Hao-Yu Liu, Shi-Da Wang, Jianbo Bai, Cheng-Lin Lv, Yue Li, Yue Shao, Xi-Qiao Feng, Bo Li","doi":"10.1038/s41567-024-02504-1","DOIUrl":null,"url":null,"abstract":"The formation of holes in epithelial tissue is essential for development, but it can also be associated with epithelial barrier dysfunction and cancer progression. Here we show that active cell contraction in epithelioid monolayer tissues derived from human embryonic stem cells can spontaneously launch a morphological transition cascade consisting of hole nucleation, coalescence and network formation. Accumulated tissue-level tensile stresses drive hole expansion from isotropic round expansion to local fracture of intercellular junctions. This is followed by fast crack propagation, which is later suppressed by the self-organized supracellular actomyosin ring and accompanied by crack blunting and a fracture-to-rounding transition. During hole coalescence, we find a fracture–slip mechanism that enables layer-by-layer breaking of the multicellular bridge but without inducing excessive cell deformation. Our multiscale theory captures these experimental observations and predicts that substrate rigidity sensing and adhesion of cells compete with cellular contraction to mediate the morphological dynamics. These findings suggest that living tissues may coordinate the mechanics across molecular, cellular and tissue scales to drive topological changes while reducing the risk of mechanical damage to cells. Active cell contraction drives hole nucleation, fracture and crack propagation in a tissue monolayer through a process reminiscent of dewetting thin films.","PeriodicalId":19100,"journal":{"name":"Nature Physics","volume":"20 8","pages":"1313-1323"},"PeriodicalIF":17.6000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Physics","FirstCategoryId":"101","ListUrlMain":"https://www.nature.com/articles/s41567-024-02504-1","RegionNum":1,"RegionCategory":"物理与天体物理","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSICS, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The formation of holes in epithelial tissue is essential for development, but it can also be associated with epithelial barrier dysfunction and cancer progression. Here we show that active cell contraction in epithelioid monolayer tissues derived from human embryonic stem cells can spontaneously launch a morphological transition cascade consisting of hole nucleation, coalescence and network formation. Accumulated tissue-level tensile stresses drive hole expansion from isotropic round expansion to local fracture of intercellular junctions. This is followed by fast crack propagation, which is later suppressed by the self-organized supracellular actomyosin ring and accompanied by crack blunting and a fracture-to-rounding transition. During hole coalescence, we find a fracture–slip mechanism that enables layer-by-layer breaking of the multicellular bridge but without inducing excessive cell deformation. Our multiscale theory captures these experimental observations and predicts that substrate rigidity sensing and adhesion of cells compete with cellular contraction to mediate the morphological dynamics. These findings suggest that living tissues may coordinate the mechanics across molecular, cellular and tissue scales to drive topological changes while reducing the risk of mechanical damage to cells. Active cell contraction drives hole nucleation, fracture and crack propagation in a tissue monolayer through a process reminiscent of dewetting thin films.
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