title: Tissue deformation spatially modulates VEGF signaling and angiogenesis.
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.
authors.affiliation: Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7500 AE Enschede, The Netherlands. nicolasrivron@gmail.com
authors.forename: Nicolas C
authors.initials: NC
authors.lastname: Rivron
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Vrij
authors.forename: Jeroen
authors.initials: J
authors.lastname: Rouwkema
authors.forename: Severine
authors.initials: S
authors.lastname: Le Gac
authors.forename: Albert
authors.initials: A
authors.lastname: van den Berg
authors.forename: Roman K
authors.initials: RK
authors.lastname: Truckenmüller
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
mesh_terms: D000199:Actins / Q000378:metabolism; D001483:Base Sequence; D001696:Biomechanical Phenomena; D018920:Coculture Techniques; D017931:DNA Primers / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D009218:Myosins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D017931:DNA Primers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D009218:Myosins