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Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration
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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.
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“perfusable microfluidic chips have also been developed to promote the long-term culture of organoids21,22,94.”
From Organoids (2022) · cites this paper as [94]
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“It has been shown that by maximizing the mass transfer and minimizing the shear stress in the perfusive soluble microenvironment, cells grown in organ-on-a-chip set-ups upregulate their functions, getting a step closer to a native tissue94,244,245.”
From Organoids (2022) · cites this paper as [94]
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Metadata
- Authors
- Pérez-González, C., Ceada, G., Greco, F., Matejčić, M., Gómez-González, M., Castro, N., Menendez, A., Kale, S., Krndija, D., Clark, A. G., Gannavarapu, V. R., Álvarez-Varela, A., Roca-Cusachs, P., Batlle, E., Vignjevic, D. M., Arroyo, M., & Trepat, X.
- Affiliations
- Barcelona Institute of Science and Technology (ES)
- Universitat Politècnica de Catalunya (ES)
- Virginia Tech (US)
- Centre National de la Recherche Scientifique (FR)
- Institute for Research in Biomedicine (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- International Center for Numerical Methods in Engineering (ES)
- Corresponding author
- Vignjevic, Danijela Matic
- Arroyo, Marino
- Trepat, Xavier
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2021-06-21
- Volume
- 23
- Issue
- 7
- Pages
- 745-757
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC7611697
- OpenAlex
- W3174575177
- Cited by
- 225
- References
- 61
- Citations by year
- 2026: 33 · 2025: 57 · 2024: 46 · 2023: 31 · 2022: 42 · 2021: 16
- FWCI
- 17.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- intestinal organoids, collective cell migration, cellular forces, extracellular matrix stiffness, stem cell compartment, transit amplifying cells, apical constriction, cell surface tension, hydrogel substrates, intestinal epithelium
- MeSH terms
- Animals, Cell Communication, Cell Movement, Cells, Cultured, Computer Simulation, Epithelial Cells, Female, Intestinal Mucosa, Male, Mice, Transgenic, Models, Biological, Organoids, Stress, Mechanical, Surface Tension, Time Factors, Microscopy, Confocal, Cell-Matrix Junctions, Mechanotransduction, Cellular
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