Microtissues®

Summary

Published in Journal of Theoretical Biology (2018), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Lakatos, Dóra, et al. Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies

❤️ Cardiovascular

Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies

Journal of Theoretical Biology 2018 Lakatos, Dóra, et al
Cite as: Lakatos, Dóra, et al. Soluble VEGFR1 signaling guides vascular patterns into dense branching morphologies. Journal of Theoretical Biology (2018). doi:10.1016/j.jtbi.2018.08.005 doi.org/10.1016/j.jtbi.2018.08.005

Research Overview

Vascular patterning is central to development and disease. The diffusible decoy receptor sVEGFR1 (sFlt1) is a known regulator of endothelial behavior, but how it controls vascular structure was little understood. This study proposes computational models of how self-organized gradients of VEGF and sVEGFR1 guide vascular patterning.

The models show that a diffusive inhibitor can generate densely branching structures when the activator drives directed growth: too little inhibitor yields compact growth, while excess inhibitor blocks expansion and stabilizes existing structures. Predictions were compared with time-resolved measurements of endothelial sprout kinetics in fibrin gels, including experiments with inhibitory antibodies against VEGFR1.

Key Discoveries

  • Computational model of vascular patterning by self-organized VEGF/sVEGFR1 gradients
  • A diffusive inhibitor produces dense branching; too little gives compact growth, too much halts expansion
  • Model predictions tested against endothelial sprout kinetics in fibrin gels with anti-VEGFR1 antibodies