1. Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration
- Author
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Gerardo Ceada, Marija Matejčić, Andrew G. Clark, Marino Arroyo, Anghara Menendez, Denis Krndija, Venkata Ram Gannavarapu, Pere Roca-Cusachs, Natalia Castro, Manuel Gomez-Gonzalez, Xavier Trepat, Adrián Álvarez-Varela, Francesco Greco, Carlos Pérez-González, Danijela Matic Vignjevic, Sohan Kale, Eduard Batlle, Universitat Politècnica de Catalunya. Centre Específic de Recerca de Mètodes Numèrics en Ciències Aplicades i Enginyeria, Universitat Politècnica de Catalunya. Departament d'Enginyeria Civil i Ambiental, and Universitat Politècnica de Catalunya. LACÀN - Mètodes Numèrics en Ciències Aplicades i Enginyeria
- Subjects
Biomatemàtica ,Crypt ,Matemàtiques i estadística::Matemàtica aplicada a les ciències [Àrees temàtiques de la UPC] ,Numerical analysis--Simulation methods ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Organoid ,Cell migration ,65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations [Classificació AMS] ,030304 developmental biology ,Biomathematics ,Anàlisi numèrica ,Intestins ,0303 health sciences ,Migració cel·lular ,Chemistry ,Matemàtiques i estadística::Anàlisi numèrica::Mètodes numèrics [Àrees temàtiques de la UPC] ,92 Biology and other natural sciences::92B Mathematical biology in general [Classificació AMS] ,Apical constriction ,Cell Biology ,Compartmentalization (psychology) ,Intestinal epithelium ,Cell biology ,Intestines ,Folding (chemistry) ,030220 oncology & carcinogenesis ,Self-healing hydrogels - Abstract
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.
- Published
- 2021