Goblet cells mechanically breach the epithelial barrier in gut homeostasis
Abstract
The intestinal epithelium forms a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal, columnar morphology, while mucus-producing goblet cells exhibit a rounded apical shape and a voluminous cell body, raising the question of how epithelial integrity is preserved in tissues with such morphological heterogeneity. Here, we show that, under homeostatic conditions in vivo, goblet cells mechanically induce tight-junction fractures between neighboring enterocytes. This effect is exacerbated by goblet cell hypertrophy and is associated with increased gut permeability. Using in vivo and organoid models, combined with pharmacological, genetic and mechanical perturbations and theoretical modeling, we demonstrate that these fractures arise from a force imbalance at cell interfaces: goblet cells exert pressure on adjacent enterocytes, whose junctional rupture depends on tissue rheology controlled by myosin II. Our findings uncover a mechanical role for goblet cells in epithelial cohesion and barrier regulation, revealing how cellular heterogeneity shapes tissue integrity.
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BibTeX
@article{creff2026goblet,
title = {{Goblet cells mechanically breach the epithelial barrier in gut homeostasis}},
author = {Justine Creff and Yuan He and Sandra Bernat-Fabre and Etienne Buscail and Salomé Neuvendel and Vishnu Krishnakumar and Dhriti Saumya and Laurent Malaquin and Thomas Mangeat and Shi-Lei Xue and Denis Krndija},
journal = {Nature Communications},
year = {2026},
month = jul,
doi = {10.1038/s41467-026-76034-0},
url = {https://hal.science/hal-05765669v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Goblet cells mechanically breach the epithelial barrier in gut homeostasis
AU - Justine Creff
AU - Yuan He
AU - Sandra Bernat-Fabre
AU - Etienne Buscail
AU - Salomé Neuvendel
AU - Vishnu Krishnakumar
AU - Dhriti Saumya
AU - Laurent Malaquin
AU - Thomas Mangeat
AU - Shi-Lei Xue
AU - Denis Krndija
PY - 2026
DA - 2026/07/25
JO - Nature Communications
DO - 10.1038/s41467-026-76034-0
UR - https://hal.science/hal-05765669v1
AB - The intestinal epithelium forms a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal, columnar morphology, while mucus-producing goblet cells exhibit a rounded apical shape and a voluminous cell body, raising the question of how epithelial integrity is preserved in tissues with such morphological heterogeneity. Here, we show that, under homeostatic conditions in vivo, goblet cells mechanically induce tight-junction fractures between neighboring enterocytes. This effect is exacerbated by goblet cell hypertrophy and is associated with increased gut permeability. Using in vivo and organoid models, combined with pharmacological, genetic and mechanical perturbations and theoretical modeling, we demonstrate that these fractures arise from a force imbalance at cell interfaces: goblet cells exert pressure on adjacent enterocytes, whose junctional rupture depends on tissue rheology controlled by myosin II. Our findings uncover a mechanical role for goblet cells in epithelial cohesion and barrier regulation, revealing how cellular heterogeneity shapes tissue integrity.
SN - 2041-1723
SN - 2041-1723
ER -