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

28 Citations (Scopus)

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

Fingerprint

Endothelial cells
Vascular Endothelial Growth Factor A
Endothelial Cells
Proteins
Fibrin
Blood vessels
Biomaterials
Assays
Integrins
Vascular Endothelial Growth Factor Receptor-2
Molecules
Intercellular Signaling Peptides and Proteins
Fibrinolysin
Biocompatible Materials
Fibronectins
Wound Healing
Blood Vessels

Keywords

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

ASJC Scopus subject areas

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

Cite this

Traub, S., Morgner, J., Martino, M. M., Höning, S., Swartz, M. A., Wickström, S. 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

The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. / Traub, Stephanie; Morgner, Jessica; Martino, Mikaël M.; Höning, Stefan; Swartz, Melody A.; Wickström, Sara A.; Hubbell, Jeffrey A.; Eming, Sabine A.

In: Biomaterials, Vol. 34, No. 24, 01.08.2013, p. 5958-5968.

Research output: Contribution to journalArticle

Traub, S, Morgner, J, Martino, MM, Höning, S, Swartz, MA, Wickström, SA, Hubbell, JA & Eming, SA 2013, 'The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165', Biomaterials, vol. 34, no. 24, pp. 5958-5968. https://doi.org/10.1016/j.biomaterials.2013.04.050
Traub S, Morgner J, Martino MM, Höning S, Swartz MA, Wickström SA et al. The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. Biomaterials. 2013 Aug 1;34(24):5958-5968. https://doi.org/10.1016/j.biomaterials.2013.04.050
Traub, Stephanie ; Morgner, Jessica ; Martino, Mikaël M. ; Höning, Stefan ; Swartz, Melody A. ; Wickström, Sara A. ; Hubbell, Jeffrey A. ; Eming, Sabine A. / The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. In: Biomaterials. 2013 ; Vol. 34, No. 24. pp. 5958-5968.
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