Goblet cells mechanically breach the epithelial barrier in gut homeostasis

Abstract The intestinal epithelium has to maintain a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells exhibit a round apical cell shape and a bulky body, raising the question of how epithelial integrity is maintained around these cells. Here, we show that goblet cells induce tight junction fractures between neighboring enterocytes under homeostatic conditions in vivo , which are exacerbated during goblet cell hypertrophy, increasing gut permeability. We demonstrate that these fractures arise from a two-component mechanical interaction: goblet cells push and deform adjacent enterocytes, which rupture depending on tissue rheology controlled by myosin II. These findings reveal that the mechanical interplay between goblet cells and neighboring enterocytes is critical for maintaining intestinal epithelial barrier integrity.

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Publication Details

Journal
Nature Communications
Published
2026-07-25
DOI
https://doi.org/10.1038/s41467-026-76034-0
Citations
3
Primary Topic
Tissue Engineering and Regenerative Medicine
Type
article
Field-Weighted Citation Impact
10.89

Funders

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article

Goblet cells mechanically breach the epithelial barrier in gut homeostasis

Denis Krndija, Laurent Malaquin, Yuan He, Sandra Bernat-Fabre et al.
3 citations
Nature Communications
Tissue Engineering and Regenerative Medicine
10.89
article

Goblet cells mechanically breach the epithelial barrier in gut homeostasis

Denis Krndija, Laurent Malaquin, Yuan He, Sandra Bernat-Fabre, V. Krishnakumar, Étienne Buscail, Justine Creff, Thomas Mangeat, Shi-Lei Xue, Salomé Neuvendel, Dhriti Saumya
article en
3 citations

Abstract

Abstract The intestinal epithelium has to maintain a tight barrier against the harsh luminal environment. Absorptive enterocytes have a polygonal and columnar shape, while mucus-producing goblet cells exhibit a round apical cell shape and a bulky body, raising the question of how epithelial integrity is maintained around these cells. Here, we show that goblet cells induce tight junction fractures between neighboring enterocytes under homeostatic conditions in vivo , which are exacerbated during goblet cell hypertrophy, increasing gut permeability. We demonstrate that these fractures arise from a two-component mechanical interaction: goblet cells push and deform adjacent enterocytes, which rupture depending on tissue rheology controlled by myosin II. These findings reveal that the mechanical interplay between goblet cells and neighboring enterocytes is critical for maintaining intestinal epithelial barrier integrity.

Nature Communications
Centre National de la Recherche Scientifique (FR), Université Toulouse III - Paul Sabatier (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Laboratoire d'Analyse et d'Architecture des Systèmes (FR), Westlake University (CN), Centre de Recherches sur la Cognition Animale (FR), Centre de Biologie du Développement (FR), Institut de Recherche en Santé Digestive (FR), Centre de Biologie Intégrative de Toulouse (FR)
Agence Nationale de la Recherche, Fondation pour la Recherche Médicale
Openalex Percentile: Top 6%
Tissue Engineering and Regenerative Medicine
10.89
DOIOpen Access PDFOpenAlex
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