Feedback between mechanosensitive signaling and active forces governs endothelial junction integrity

Area of Science:

• Biophysics
• Cell Biology
• Vascular Biology

Background:

• Endothelial gap formation and recovery are crucial in physiological and pathological processes, including angiogenesis and tumor metastasis.
• The complex interplay between mechanical forces and signaling pathways regulating vascular endothelial cell dynamics remains poorly understood.

Purpose of the Study:

• To develop a chemo-mechanical model investigating the regulation of endothelial junctions.
• To explore the feedback mechanisms between actomyosin contractility, VE-cadherin bond dynamics, and actin polymerization in mediating cell-cell interface forces.

Main Methods:

• Development of a computational chemo-mechanical model.
• Simulations of endothelial junction dynamics under varying signaling conditions (RhoA, Rac1).
• Integration of the modeling framework with experimental data to predict treatment effects.

Main Results:

• Active cell tension can stabilize VE-cadherin bonds, but excessive RhoA signaling leads to junction failure.
• Actin polymerization promotes gap closure, yet high Rac1 levels can weaken endothelial junctions.
• A critical balance between RhoA and Rac1 signaling is essential for maintaining junction stability.

Conclusions:

• The model accurately predicts the influence of pharmacological interventions on endothelial junction states.
• This framework provides insights into maintaining vascular integrity and suggests therapeutic strategies targeting Rho GTPases.