Xiangjun Peng, Yuxuan Huang, Wenyu Kong, Yanan Du, Elliot L. Elson, Xi-Qiao Feng, Guy M. Genin
{"title":"在基质介导的组织重构中,纤维募集在一个关键的细胞间距上驱动细胞极化的相变","authors":"Xiangjun Peng, Yuxuan Huang, Wenyu Kong, Yanan Du, Elliot L. Elson, Xi-Qiao Feng, Guy M. Genin","doi":"10.1073/pnas.2514995122","DOIUrl":null,"url":null,"abstract":"Biological tissues exhibit sharp phase transitions where cells collectively transition from disordered to ordered states at critical densities. We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from a nonmonotonic dependence on nonlinear extracellular matrix (ECM) mechanics: mechanical communication between cells is optimized at intermediate stiffness values where cells can both generate sufficient forces and create strain-stiffened tension bands in the ECM. This balance establishes a critical cell spacing threshold for cell–cell communication ( <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mo>∼</mml:mo> </mml:math> </jats:inline-formula> 100 to 200 <jats:inline-formula> <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\" display=\"inline\" overflow=\"scroll\"> <mml:mi mathvariant=\"normal\">μ</mml:mi> </mml:math> </jats:inline-formula> m) that is conserved across experimental observations for a broad range of cell types and collagen densities. Our model reveals that the critical stretch ratio at which fibrous networks transition from compliant to strain-stiffening governs this threshold through the formation of tension bands between neighboring cells. These mechanical communication networks drive collective phase transition in tissue condensation when cell density exceeds an effective percolation threshold. Our model explains how microscale cell–ECM interactions control emergent mechanical properties in biological systems and offers insight both into the physics of inhomogeneous materials under active stress, and into potential mechanical interventions for wound healing and fibrotic disorders.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"20 1","pages":""},"PeriodicalIF":9.1000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fiber recruitment drives a phase transition of cell polarization at a critical cell spacing in matrix-mediated tissue remodeling\",\"authors\":\"Xiangjun Peng, Yuxuan Huang, Wenyu Kong, Yanan Du, Elliot L. Elson, Xi-Qiao Feng, Guy M. Genin\",\"doi\":\"10.1073/pnas.2514995122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Biological tissues exhibit sharp phase transitions where cells collectively transition from disordered to ordered states at critical densities. We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from a nonmonotonic dependence on nonlinear extracellular matrix (ECM) mechanics: mechanical communication between cells is optimized at intermediate stiffness values where cells can both generate sufficient forces and create strain-stiffened tension bands in the ECM. This balance establishes a critical cell spacing threshold for cell–cell communication ( <jats:inline-formula> <mml:math xmlns:mml=\\\"http://www.w3.org/1998/Math/MathML\\\" display=\\\"inline\\\" overflow=\\\"scroll\\\"> <mml:mo>∼</mml:mo> </mml:math> </jats:inline-formula> 100 to 200 <jats:inline-formula> <mml:math xmlns:mml=\\\"http://www.w3.org/1998/Math/MathML\\\" display=\\\"inline\\\" overflow=\\\"scroll\\\"> <mml:mi mathvariant=\\\"normal\\\">μ</mml:mi> </mml:math> </jats:inline-formula> m) that is conserved across experimental observations for a broad range of cell types and collagen densities. Our model reveals that the critical stretch ratio at which fibrous networks transition from compliant to strain-stiffening governs this threshold through the formation of tension bands between neighboring cells. These mechanical communication networks drive collective phase transition in tissue condensation when cell density exceeds an effective percolation threshold. Our model explains how microscale cell–ECM interactions control emergent mechanical properties in biological systems and offers insight both into the physics of inhomogeneous materials under active stress, and into potential mechanical interventions for wound healing and fibrotic disorders.\",\"PeriodicalId\":20548,\"journal\":{\"name\":\"Proceedings of the National Academy of Sciences of the United States of America\",\"volume\":\"20 1\",\"pages\":\"\"},\"PeriodicalIF\":9.1000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the National Academy of Sciences of the United States of America\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1073/pnas.2514995122\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the National Academy of Sciences of the United States of America","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1073/pnas.2514995122","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Fiber recruitment drives a phase transition of cell polarization at a critical cell spacing in matrix-mediated tissue remodeling
Biological tissues exhibit sharp phase transitions where cells collectively transition from disordered to ordered states at critical densities. We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from a nonmonotonic dependence on nonlinear extracellular matrix (ECM) mechanics: mechanical communication between cells is optimized at intermediate stiffness values where cells can both generate sufficient forces and create strain-stiffened tension bands in the ECM. This balance establishes a critical cell spacing threshold for cell–cell communication ( ∼ 100 to 200 μ m) that is conserved across experimental observations for a broad range of cell types and collagen densities. Our model reveals that the critical stretch ratio at which fibrous networks transition from compliant to strain-stiffening governs this threshold through the formation of tension bands between neighboring cells. These mechanical communication networks drive collective phase transition in tissue condensation when cell density exceeds an effective percolation threshold. Our model explains how microscale cell–ECM interactions control emergent mechanical properties in biological systems and offers insight both into the physics of inhomogeneous materials under active stress, and into potential mechanical interventions for wound healing and fibrotic disorders.
期刊介绍:
The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.