Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration
Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forc...
| Autores: | , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2021 |
| País: | España |
| Recursos: | Universitat Politècnica de Catalunya (UPC) |
| Repositório: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglês |
| OAI Identifier: | oai:upcommons.upc.edu:2117/355120 |
| Acesso em linha: | https://hdl.handle.net/2117/355120 https://dx.doi.org/10.1038/s41556-021-00699-6 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Numerical analysis--Simulation methods Biomathematics Anàlisi numèrica Biomatemàtica Classificació AMS::65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general Àrees temàtiques de la UPC::Matemàtiques i estadística::Anàlisi numèrica::Mètodes numèrics Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències |
| Resumo: | Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the extracellular matrix and folds through apical constriction, whereas the transit amplifying zone pulls the extracellular matrix and elongates through basal constriction. The size of the stem cell compartment depends on the extracellular-matrix stiffness and endogenous cellular forces. Computational modelling reveals that crypt shape and force distribution rely on cell surface tensions following cortical actomyosin density. Finally, cells are pulled out of the crypt along a gradient of increasing tension. Our study unveils how patterned forces enable compartmentalization, folding and collective migration in the intestinal epithelium. |
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