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Biomechanical control of vascular morphogenesis by the surrounding stiffness
Yasuyuki Hanada1,2,3, Semanti Halder1, Yuichiro Arima2
1Laboratory for Vascular and Cellular Dynamics, Department of Medical Sciences, University of Miyazaki, Miyazaki, Miyazaki, Japan.
Nature Communications
|July 28, 2025
Summary
Perivascular stiffening, regulated by pericytes and collagen-IV deposition, integrates blood vessel branch elongation and lumen expansion during angiogenesis. This process ensures coordinated development of vascular networks.
Area of Science:
- Vascular biology
- Cellular morphogenesis
- Biophysics
Background:
- Sprouting angiogenesis expands vascular networks from existing vessels.
- The mechanisms coordinating endothelial cell (EC) movement for branch elongation and lumen development under blood flow are unclear.
Purpose of the Study:
- To elucidate the role of perivascular stiffening in integrating branch elongation and lumen development during angiogenesis.
- To investigate how pericytes and extracellular matrix components influence these processes.
Main Methods:
- Investigated the interplay between endothelial cells, pericytes, and the vascular basement membrane.
- Analyzed the impact of perivascular stiffness on endothelial cell behavior and lumen formation.
- Examined the localization of F-BAR proteins and Arp2/3 complexes in tip ECs.
Main Results:
- Perivascular stiffening, induced by pericyte-mediated collagen-IV deposition, integrates branch elongation and lumen development.
- Lumen expansion inhibits directional EC movement, a process counter-regulated by pericytes.
- Reduced forward movement of tip ECs correlates with decreased F-BAR and Arp2/3 complex localization.
Conclusions:
- Perivascular stiffening is a key factor coordinating EC-driven branch elongation and lumen development in angiogenesis.
- Pericytes play a crucial role in regulating vascular architecture by modulating perivascular stiffness.
- Proper physical environment construction, in coordination with pericytes, is essential for angiogenesis.
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