Partial epithelial-to-mesenchymal transition mediates profound gap closure through growth and fluidization

Area of Science:

• Cell biology
• Biophysics
• Developmental biology

Background:

• Epithelial gap closure is vital for tissue integrity, development, and wound healing.
• Small gap closure relies on actomyosin contraction and edge traction forces.
• Mechanisms for large-scale gap closure remain less understood.

Purpose of the Study:

• To investigate the primary drivers of millimeter-scale circular epithelial gap closure in mouse epicardial (MEC1) monolayers.
• To compare the closure dynamics of MEC1 cells with other epithelial models like MDCK cells.
• To elucidate the cellular and tissue-level mechanisms governing large-scale gap closure.

Main Methods:

• Tissue and cell kinematic analysis
• Traction-force mapping
• Continuum framework to decompose tissue strain rates (growth, elastic, fluid)
• Modulation experiments using epithelial-mesenchymal transition induction and Rho kinase inhibition

Main Results:

• Millimeter-scale gap closure in MEC1 monolayers is primarily driven by growth-mediated compressive stresses.
• MEC1 cells exhibit faster gap closure with reduced edge undulation compared to MDCK cells, through coordinated tissue-wide extension-contraction.
• Growth-generated compression drives inward tissue flow, complemented by elastic cell elongation and fluid-like remodeling via cell intercalation.

Conclusions:

• Growth-mediated compression is a key mechanism for large-scale epithelial gap closure.
• Synergistic contributions of growth, elastic deformation, and fluid remodeling enable robust collective tissue repair.
• Understanding these dynamics offers insights into developmental processes and therapeutic strategies for wound healing.