Dynamics of VEGF matrix-retention in vascular network patterning

A. Köhn-Luque, W. De Back, Y. Yamaguchi, K. Yoshimura, M. A. Herrero, T. Miura

研究成果: Contribution to journalArticle査読

27 被引用数 (Scopus)

抄録

Vascular endothelial growth factor (VEGF) is a central regulator of blood vessel morphogenesis, although its role in patterning of endothelial cells into vascular networks is not fully understood. It has been suggested that binding of soluble VEGF to extracellular matrix components causes spatially restricted cues that guide endothelial cells into network patterns. Yet, current evidence for such a mechanism remains indirect. In this study, we quantitatively analyse the dynamics of VEGF retention in a controlled in vitro situation of human umbilical vascular endothelial cells (HUVECs) in Matrigel. We show that fluorescent VEGF accumulates in pericellular areas and colocalizes with VEGF binding molecules. Analysis of fluorescence recovery after photobleaching reveals that binding/unbinding to matrix molecules dominates VEGF dynamics in the pericellular region. Computational simulations using our experimental measurements of kinetic parameters show that matrix retention of chemotactic signals can lead to the formation of reticular cellular networks on a realistic timescale. Taken together, these results show that VEGF binds to matrix molecules in proximity of HUVECs in Matrigel, and suggest that bound VEGF drives vascular network patterning.

本文言語英語
論文番号066007
ジャーナルPhysical Biology
10
6
DOI
出版ステータス出版済み - 12 2013

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 構造生物学
  • 分子生物学
  • 細胞生物学

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