Tissue geometry patterns epithelial-mesenchymal transition via intercellular mechanotransduction.

Area of Science:

• Cell Biology
• Biophysics
• Developmental Biology

Background:

• Epithelial-mesenchymal transition (EMT) is a critical cellular process involving loss of cell-cell adhesion and increased motility.
• While soluble factors like growth factors and cytokines are known EMT inducers, the spatial regulation of EMT remains incompletely understood.

Purpose of the Study:

• To investigate the role of mechanical stress and tissue geometry in spatially patterning epithelial-mesenchymal transition (EMT).
• To identify the molecular mechanisms linking mechanical cues to EMT induction.

Main Methods:

• Utilized mammary epithelial cell sheets cultured in vitro.
• Applied transforming growth factor-beta (TGF-β) to induce EMT.
• Employed traction force microscopy and finite element modeling to quantify mechanical stress.
• Assessed expression of EMT markers and localization of myocardin-related transcription factor A (MRTF-A).

Main Results:

• EMT markers were predominantly expressed at the corners and edges of epithelial sheets, not the center.
• Altering epithelial sheet geometry changed the spatial distribution of EMT.
• Regions of high mechanical stress correlated with EMT occurrence and MRTF-A nuclear localization.
• Inhibition of cytoskeletal tension or MRTF-A disrupted EMT spatial patterning.

Conclusions:

• Tissue geometry and endogenous mechanical stresses are critical determinants of EMT spatial localization.
• Mechanical stress, mediated by MRTF-A, plays a causal role in patterning EMT.
• This highlights a novel mechanism for controlling cell fate decisions based on physical cues.