Tight junctions control lumen morphology via hydrostatic pressure and junctional tension

Area of Science:

• Cell biology
• Biophysics
• Developmental biology

Background:

• Epithelial tissues form fluid-filled lumina crucial for organ development.
• The precise mechanical mechanisms by which cells control lumen morphology are not fully understood.

Purpose of the Study:

• To quantify the mechanical role of tight junctions in epithelial lumen formation.
• To elucidate the interplay between hydraulic pressure, cortical tension, and junctional integrity.

Main Methods:

• Utilized Madin-Darby canine kidney II (MDCK-II) cysts to model lumen formation.
• Quantified hydrostatic lumen pressure and junctional tension.
• Employed computational modeling to analyze force balance and lumen morphology.

Main Results:

• The paracellular ion barrier function of claudin receptors is not essential for lumen inflation.
• Depletion of the zonula occludens scaffold led to lumen collapse and apical membrane folding.
• Tight junctions decrease cortical tension by inhibiting myosin, promoting lumen inflation.
• Excess apical surface area appears to contribute to lumen opening.

Conclusions:

• Tight junctions play a critical mechanical role in epithelial lumen formation and stability.
• A balance between hydrostatic pressure and junctional tension governs lumen morphology.
• Epithelial cells actively modulate tissue shape through tight junction-mediated force regulation.