Tissue deformation spatially modulates VEGF signaling and angiogenesis

Nicolas C. Rivron, Erik J. Vrij, Jeroen Rouwkema, Severine le Gac, Albert van den Berg, Roman K. Truckenmüller, Clemens A. van Blitterswijk

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Physical forces play a major role in the organization of developing tissues. During vascular development, physical forces originating from a fluid phase or from cells pulling on their environment can alter cellular signaling and the behavior of cells. Here, we observe how tissue deformation spatially modulates angiogenic signals and angiogenesis. Using soft lithographic templates, we assemble three-dimensional, geometric tissues. The tissues contract autonomously, change shape stereotypically and form patterns of vascular structures in regions of high deformations. We show that this emergence correlates with the formation of a long-range gradient of Vascular Endothelial Growth Factor (VEGF) in interstitial cells, the local overexpression of the corresponding receptor VEGF receptor 2 (VEGFR-2) and local differences in endothelial cells proliferation. We suggest that tissue contractility and deformation can induce the formation of gradients of angiogenic microenvironments which could contribute to the long-range patterning of the vascular system.
Original languageEnglish
Pages (from-to)6886-6891
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number18
DOIs
Publication statusPublished - 1 May 2012

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Vascular Endothelial Growth Factor A
Blood Vessels
Vascular Endothelial Growth Factor Receptor-2
Endothelial Cells
Cell Proliferation

Keywords

  • METIS-286389
  • EWI-21917
  • IR-80519

Cite this

Rivron, Nicolas C. ; Vrij, Erik J. ; Rouwkema, Jeroen ; le Gac, Severine ; van den Berg, Albert ; Truckenmüller, Roman K. ; van Blitterswijk, Clemens A. / Tissue deformation spatially modulates VEGF signaling and angiogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 18. pp. 6886-6891.
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Tissue deformation spatially modulates VEGF signaling and angiogenesis. / Rivron, Nicolas C.; Vrij, Erik J.; Rouwkema, Jeroen ; le Gac, Severine ; van den Berg, Albert ; Truckenmüller, Roman K.; van Blitterswijk, Clemens A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 18, 01.05.2012, p. 6886-6891.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Tissue deformation spatially modulates VEGF signaling and angiogenesis

AU - Rivron, Nicolas C.

AU - Vrij, Erik J.

AU - Rouwkema, Jeroen

AU - le Gac, Severine

AU - van den Berg, Albert

AU - Truckenmüller, Roman K.

AU - van Blitterswijk, Clemens A.

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AB - Physical forces play a major role in the organization of developing tissues. During vascular development, physical forces originating from a fluid phase or from cells pulling on their environment can alter cellular signaling and the behavior of cells. Here, we observe how tissue deformation spatially modulates angiogenic signals and angiogenesis. Using soft lithographic templates, we assemble three-dimensional, geometric tissues. The tissues contract autonomously, change shape stereotypically and form patterns of vascular structures in regions of high deformations. We show that this emergence correlates with the formation of a long-range gradient of Vascular Endothelial Growth Factor (VEGF) in interstitial cells, the local overexpression of the corresponding receptor VEGF receptor 2 (VEGFR-2) and local differences in endothelial cells proliferation. We suggest that tissue contractility and deformation can induce the formation of gradients of angiogenic microenvironments which could contribute to the long-range patterning of the vascular system.

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