Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration.
Nat Cell Biol
; 23(7): 745-757, 2021 07.
Article
en En
| MEDLINE
| ID: mdl-34155382
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Mecanotransducción Celular
/
Células Epiteliales
/
Mucosa Intestinal
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Cell Biol
Año:
2021
Tipo del documento:
Article