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A mechanical modeling framework to study endothelial permeability.

Pradeep Keshavanarayana1, Fabian Spill1

  • 1School of Mathematics, University of Birmingham, Birmingham, United Kingdom.

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This summary is machine-generated.

This study models how mechanical forces and chemical signals affect blood vessel permeability by examining VE-cadherin bonds. Mechanochemical modeling reveals how cell junctions and substrate stiffness influence particle passage, crucial for understanding diseases.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Mechanobiology

Background:

  • Endothelial cells form the blood vessel lining, regulating permeability via VE-cadherin bonds.
  • Abnormal endothelial permeability is linked to diseases like cardiovascular disease, cancer, and COVID-19.
  • Simultaneous effects of mechanical and chemical stimuli on endothelial permeability are not fully understood.

Purpose of the Study:

  • To develop a continuum-level mechanical modeling framework for dynamic VE-cadherin bonds.
  • To investigate the role of the actin cytoskeleton and substrate in endothelial permeability.
  • To understand how combined mechanical and chemical stimuli influence endothelial barrier function.

Main Methods:

  • Modeled VE-cadherin bonds using cohesive contact with damage and a traction-separation law.
  • Incorporated actin cytoskeleton and substrate mechanics into the model.
  • Developed a contact mechanics-based mechanochemical model.

Main Results:

  • Mechanochemical coupling is essential for simulating substrate mechanical property influences on permeability.
  • Cellular shear explains permeability differences between bicellular and tricellular junctions.
  • Increased traction force and substrate stiffness elevate endothelial permeability.

Conclusions:

  • The model elucidates the dynamic regulation of endothelial permeability by mechanical and chemical cues.
  • Mechanochemical interactions are critical for substrate-dependent permeability.
  • Monolayer geometry (cylindrical vs. planar) affects overall permeability.