期刊
NATURE CELL BIOLOGY
卷 23, 期 7, 页码 745-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41556-021-00699-6
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资金
- Spanish Ministry for Science, Innovation and Universities MICCINN/FEDER [PGC2018-099645-B-I00, PID2019-110949GB-I00]
- Generalitat de Catalunya (Agaur) [SGR-2017-01602, 2017-SGR-1278, 2017-SGR-698]
- European Research Council [Adv-883739, CoG-681434, CoG-772487]
- European Union [H2020-FETPROACT-01-2016-731957]
- Marie Skodowska-Curie grant [797621, 792028]
- 'La Caixa' Foundation [LCF/PR/HR20/52400004, 100010434, LCF/BQ/DR19/11740013, LCF/BQ/DE14/10320008, 01/16/FLC]
- Spanish Ministry of Health [SAF2017-86782-R]
- Fundacio la Marato de TV3 [201903-30-31-32]
- MINECO
- CERCA Programme
- 'ICREA Academia' award
- Marie Curie Actions (MSCA) [797621, 792028] Funding Source: Marie Curie Actions (MSCA)
Intestinal organoids exhibit non-monotonic stress distribution, with distinct mechanical domains affecting cell folding and migration along a gradient of increasing tension.
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. Perez-Gonzalez et al. explore the mechanical properties of intestinal organoids, and report the existence of distinct mechanical domains and that cells are pulled out of the central crypt along a gradient of increasing tension.
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