PRINCIPLES GOVERNING ENDOTHELIAL CAVEOLAE ORGANIZATION DURING ANGIOGENESIS.

Area of Science:

• Cell Biology
• Biophysics
• Vascular Biology

Background:

• Caveolae are flask-shaped invaginations in endothelial cells crucial for membrane tension buffering.
• The spatial organization principles of caveolae within endothelial cells remain largely unknown.
• Understanding caveolae organization is key to deciphering their role in vascular function.

Purpose of the Study:

• To systematically analyze the spatial organization of caveolae in endothelial cells under defined biophysical constraints.
• To develop a high-fidelity framework for understanding caveolae distribution in various cellular and in vivo contexts.
• To correlate caveolae arrangement with endothelial cell migration, polarity, and vascular remodeling.

Main Methods:

• Utilized micropatterning technologies to control endothelial cell geometry and biophysical environments.
• Integrated experiments with a high-throughput spatial cell mapping computational pipeline.
• Analyzed thousands of caveolae across diverse experimental conditions, including in vivo angiogenic vasculature.

Main Results:

• Caveolae preferentially localize to the rear of migrating and polarized endothelial cells.
• In monolayer configurations, caveolae exhibit a default peri-junctional spatial organization.
• In vivo, caveolae are prominent at the vascular front in response to vascular endothelial growth factor (VEGF) signaling.

Conclusions:

• Caveolae spatial arrangement is governed by cellular migration, polarity, and confinement levels.
• Caveolae distribution is dynamically regulated by signaling pathways like VEGF.
• The cellular arrangement and number of caveolae predict vascular stability and remodeling states.