Generation of fate patterns via intercellular forces

Studies of fate patterning during development typically emphasize cell-cell communication via diffusible chemical signals. Recent experiments on stem cell colonies, however, suggest that in some cases mechanical stresses, rather than secreted chemicals, enable long-ranged cell-cell interactions that...

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Main Authors: Hayden Nunley, Xufeng Xue, Jianping Fu, David K. Lubensky
Format: Article
Language:English
Published: American Physical Society 2025-06-01
Series:Physical Review Research
Online Access:http://doi.org/10.1103/PhysRevResearch.7.L022051
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author Hayden Nunley
Xufeng Xue
Jianping Fu
David K. Lubensky
author_facet Hayden Nunley
Xufeng Xue
Jianping Fu
David K. Lubensky
author_sort Hayden Nunley
collection DOAJ
description Studies of fate patterning during development typically emphasize cell-cell communication via diffusible chemical signals. Recent experiments on stem cell colonies, however, suggest that in some cases mechanical stresses, rather than secreted chemicals, enable long-ranged cell-cell interactions that specify positional information and pattern cell fates. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony edge, more contractile than cells at the center, seed a pattern that propagates via force transmission. Strikingly, our model implies that the width of the outer fate domain varies nonmonotonically with substrate stiffness, a prediction that we confirm experimentally; we argue that a similar dependence on substrate stiffness can be achieved by a chemical morphogen only if strong constraints on the signaling pathway's mechanobiology are met. Our findings thus support the idea that mechanical stress can mediate patterning in the complete absence of chemical morphogens, even in nonmotile cell layers, thus expanding the repertoire of possible roles for mechanical signals in development and morphogenesis. Future tests of additional model predictions, like the effect of anisotropic substrate rigidity, will further broaden the range of achievable fate patterns.
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spelling doaj-art-918444df31dc4e26980a57872eae0d4b2025-08-20T03:07:41ZengAmerican Physical SocietyPhysical Review Research2643-15642025-06-0172L02205110.1103/PhysRevResearch.7.L022051Generation of fate patterns via intercellular forcesHayden NunleyXufeng XueJianping FuDavid K. LubenskyStudies of fate patterning during development typically emphasize cell-cell communication via diffusible chemical signals. Recent experiments on stem cell colonies, however, suggest that in some cases mechanical stresses, rather than secreted chemicals, enable long-ranged cell-cell interactions that specify positional information and pattern cell fates. These findings inspire a model of mechanical patterning: fate affects cell contractility, and pressure in the cell layer biases fate. Cells at the colony edge, more contractile than cells at the center, seed a pattern that propagates via force transmission. Strikingly, our model implies that the width of the outer fate domain varies nonmonotonically with substrate stiffness, a prediction that we confirm experimentally; we argue that a similar dependence on substrate stiffness can be achieved by a chemical morphogen only if strong constraints on the signaling pathway's mechanobiology are met. Our findings thus support the idea that mechanical stress can mediate patterning in the complete absence of chemical morphogens, even in nonmotile cell layers, thus expanding the repertoire of possible roles for mechanical signals in development and morphogenesis. Future tests of additional model predictions, like the effect of anisotropic substrate rigidity, will further broaden the range of achievable fate patterns.http://doi.org/10.1103/PhysRevResearch.7.L022051
spellingShingle Hayden Nunley
Xufeng Xue
Jianping Fu
David K. Lubensky
Generation of fate patterns via intercellular forces
Physical Review Research
title Generation of fate patterns via intercellular forces
title_full Generation of fate patterns via intercellular forces
title_fullStr Generation of fate patterns via intercellular forces
title_full_unstemmed Generation of fate patterns via intercellular forces
title_short Generation of fate patterns via intercellular forces
title_sort generation of fate patterns via intercellular forces
url http://doi.org/10.1103/PhysRevResearch.7.L022051
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AT xufengxue generationoffatepatternsviaintercellularforces
AT jianpingfu generationoffatepatternsviaintercellularforces
AT davidklubensky generationoffatepatternsviaintercellularforces