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

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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

    Fingerprint

    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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    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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