The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165

Stephanie Traub, Jessica Morgner, Mikaël M. Martino, Stefan Höning, Melody A. Swartz, Sara A. Wickström, Jeffrey A. Hubbell, Sabine A. Eming

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Synergy in the downstream signaling pathways of the vascular endothelial growth factor receptor-2 (VEGFR-2) and the integrin αvβ3 is critical for blood vessel formation. Thus, agents that activate both receptors could possess efficient pro-angiogenic potential. Here, we created a fibrin-binding bi-functional protein (FNIII10-VEGF) consisting of the 10th type III domain of fibronectin (FNIII10) fused to a plasmin-resistant VEGF-A165 mutant (VEGF) that potentiated angiogenic processes when compared to the effect of the separate molecules. FNIII10-VEGF was able to bind both VEGFR-2 and integrin αvβ3. Intriguingly, cell attachment and spreading to immobilized FNIII10-VEGF was significantly enhanced compared to individual FNIII10 or VEGF proteins. Delivery of immobilized FNIII10-VEGF by covalent linkage to a fibrin matrix significantly enhanced the angiogenic response in an invivo wound healing assay compared to soluble VEGF. Unexpectedly, the angiogenic response to fibrin-immobilized FNIII10-VEGF was reduced in comparison to the pro-angiogenic effect of fibrin-immobilized VEGF. Collectively, findings of this study corroborate a critical role for a subtle balance of the integrin-VEGF interplay in angiogenesis and provide insight in how engineered growth factors in concert with biomaterial matrices may offer a potent molecular/material approach to harness these interactions for therapeutic angiogenesis.

Original languageEnglish (US)
Pages (from-to)5958-5968
Number of pages11
JournalBiomaterials
Volume34
Issue number24
DOIs
StatePublished - Aug 1 2013

Keywords

  • Adhesion
  • Angiogenesis
  • Cell spreading
  • Fibronectin
  • Integrins
  • VEGF

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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    Traub, S., Morgner, J., Martino, M. M., Höning, S., Swartz, M. A., Wickström, S. A., Hubbell, J. A., & Eming, S. A. (2013). The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. Biomaterials, 34(24), 5958-5968. https://doi.org/10.1016/j.biomaterials.2013.04.050