Issue 22, 2010

Matrix density mediates polarization and lumen formation of endothelial sprouts in VEGF gradients

Abstract

Endothelial cell (EC) sprouting morphogenesis is a critical step during angiogenesis, the formation of new blood vessels from existing conduits. Here, three-dimensional sprouting morphogenesis was examined using in vitro microfluidic devices that enabled the separate and simultaneous tuning of biomechanical and soluble biochemical stimuli. Quantitative analysis of endothelial sprout formation demonstrated that the ability of vascular endothelial growth factor (VEGF) to regulate stable sprout formation was mediated by the density of the surrounding collagen/fibronectin matrix. The coordinated migration and proliferation of multiple ECs to form stable sprouts were enhanced at intermediate matrix densities (1.2–1.9 mg ml−1), while lower densities resulted in uncoordinated migration (0.3–0.7 mg ml−1) and higher densities resulted in broad cell clusters that did not elongate (2.7 mg ml−1). Within the permissive range of matrix biomechanics, higher density matrices resulted in shorter, thicker, and slower-growing sprouts. The sprouts in higher density matrices also were more likely to polarize towards higher VEGF concentrations, included more cells per cross-sectional area, and demonstrated more stable lumen formation compared to sprouts in lower density matrices. These results quantitatively demonstrate that matrix density mediates VEGF-induced sprout polarization and lumen formation, potentially by regulating the balance between EC migration rate and proliferation rate.

Graphical abstract: Matrix density mediates polarization and lumen formation of endothelial sprouts in VEGF gradients

Supplementary files

Article information

Article type
Paper
Submitted
13 Apr 2010
Accepted
26 Jul 2010
First published
01 Sep 2010

Lab Chip, 2010,10, 3061-3068

Matrix density mediates polarization and lumen formation of endothelial sprouts in VEGF gradients

A. Shamloo and S. C. Heilshorn, Lab Chip, 2010, 10, 3061 DOI: 10.1039/C005069E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements