Thanks, Bertrand! We just thought it’s time to give faeces the mechanical respect it deserves! 💪💩

Amazing work by Vishnu & the MechanoGut team! 💩⚙️🛠️ Huge thanks to @cbitoulouse.bsky.social imaging & animal facilities, our dear colleagues and collaborators, and funders @cnrs.fr ATIP-Avenir, ED-BSB, @frm-officiel.bsky.social
#Mechanobiology #GutBarrier #EpithelialBiology #CellAdhesion

Pathologically, when this adaptive capacity is exceeded – as in IBD, fibrotic strictures, obstruction, or toxic megacolon – barrier failure and inflammation may ensue. Understanding these mechanisms could inform new strategies to restore epithelial integrity in disease.

Our findings resonate with work from A. Yap, A. Miller, K. Green, C. Niessen, G. Charras and others on how junctional tension and cytoskeletal coupling sustain epithelial resilience. We reveal that such mechano-adaptive coordination also operates in vivo, in an adult organ under mechanical stress.

Also, this work sheds more light on the unexpected dynamics of desmosomes and intermediate filaments – long seen as static anchors, now increasingly recognised as mechano-responsive players in epithelial resilience!

🧠 Take-home:
The gut epithelium isn’t a passive barrier – it’s relentlessly adaptive.
Extrinsic forces from faeces trigger a rapid, coordinated reinforcement of all junctional complexes, preserving barrier function and homeostasis under continuous stress 💩💪 (11/11)

Using a luminal-accessibility assay for E-cadherin, we found that depleting NMIIA in vivo or inhibiting myosin II / Ca²⁺ influx ex vivo led to barrier breaches under mechanical stress.
The junctional response is therefore essential for maintaining epithelial integrity (10/11)

Conversely, activating Piezo1 was enough to trigger NMII activation and junctional recruitment.
👉 Mechanosensitive Ca²⁺ influx is both necessary and sufficient for junctional reinforcement under force ⚡️(9/11)

💡 What activates myosin II under mechanical stress?
Blocking mechanosensitive ion channels (with Gd³⁺) or chelating extracellular Ca²⁺ (with BAPTA) prevented NMII activation and junctional reinforcement – stopping the mechano-adaptive response in its tracks (8/11)

Genetic deletion (Myh9-KO in vivo) or pharmacological inhibition of NMII ex vivo abolished junctional recruitment across all complexes.
👉 NMII acts as a central effector coordinating force sensing and junctional reinforcement.🔩 (7/11)

Junctional reinforcement coincided with recruitment of myosin IIA (NMIIA) to perijunctional belts and transient apical constriction – hallmarks of contractile activation.
Unexpectedly, myosin IIC, usually linked to microvilli, also relocalized to junctions under force ⚙️ (6/11)

Using a controlled in vivo colonic distension system (with Nicolas Cenac, IRSD Toulouse), we uncovered two kinetic modes:
- Tight & adherens junctions → sustained reinforcement
- Desmosomes & keratin filaments → progressive accumulation over time (5/11)

This mucosal remodelling comes with striking reinforcement of tight, adherens, and desmosomal junctions – a robust, pan-junctional mechano-adaptive response.
The adult gut epithelium actively adapts to physiological mechanical stress 💪 (4/11)

💩 Faeces matter – mechanically!
Most studies remove luminal contents before analysis – we didn’t.
Keeping them revealed that the colonic mucosa adapts to faecal distension through large-scale tissue unfolding and epithelial deformation (3/11)

Mechanical forces shape tissues throughout development and physiology – yet in vivo evidence for mechano-adaptation in adult organs remains scarce.
The colon must regularly accommodate voluminous faeces, but how it adapts to this load while maintaining barrier integrity was unknown (2/11)