VE-Cadherin-Actin Regulation Promotes Mechanotransduction and Monolayer Maturation Involving a Tension-Sensitive...

Area of Science:

• Cell Biology
• Biophysics

Background:

• Epithelial and endothelial monolayers maintain homeostasis through complex adaptive processes.
• The molecular regulation of monolayer maturation and mechanotransduction remains incompletely understood.

Purpose of the Study:

• To elucidate the molecular regulation of endothelial monolayer maturation and mechanotransduction-induced remodeling.
• To identify novel intermediate states in endothelial cell adaptation to mechanical stimuli.

Main Methods:

• Utilized human umbilical vein endothelial cell (HUVEC) cultures.
• Investigated molecular changes during monolayer maturation and response to shear stress using mechanotransduction.
• Analyzed junctional protein dynamics (VE-cadherin, actin, integrins, vinculin) and actomyosin tension (MLC phosphorylation).

Main Results:

• Monolayer maturation involves reduced cell perimeter and increased junctional VE-cadherin, actin, integrins, and vinculin for stability.
• Identified a novel, rapid, and reversible intermediate state characterized by VE-cadherin linearization and actomyosin relaxation (MLC dephosphorylation) under mechanical load.
• This intermediate state enhances barrier function and protects cells, while subsequent MLC rephosphorylation drives cell shape change and remodeling via JAIL formation.

Conclusions:

• Endothelial cell adaptation involves a tension-sensitive intermediate state regulated by VE-cadherin and actomyosin signaling.
• This state protects endothelial cells from mechanical damage and primes them for remodeling.
• The findings provide a comprehensive model for endothelial mechanotransduction and stress adaptation.