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 language | English |
|---|---|
| Pages (from-to) | 5958-5968 |
| Number of pages | 11 |
| Journal | Biomaterials |
| Volume | 34 |
| Issue number | 24 |
| DOIs | |
| State | Published - Aug 1 2013 |
| Externally published | Yes |
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Keywords
- Adhesion
- Angiogenesis
- Cell spreading
- Fibronectin
- Integrins
- VEGF
ASJC Scopus subject areas
- Biomaterials
- Bioengineering
- Ceramics and Composites
- Mechanics of Materials
- Biophysics
Cite this
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 journal › Article
}
TY - JOUR
T1 - The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165
AU - Traub, Stephanie
AU - Morgner, Jessica
AU - Martino, Mikaël M.
AU - Höning, Stefan
AU - Swartz, Melody A.
AU - Wickström, Sara A.
AU - Hubbell, Jeffrey A.
AU - Eming, Sabine A.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
KW - Adhesion
KW - Angiogenesis
KW - Cell spreading
KW - Fibronectin
KW - Integrins
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84878114080&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878114080&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.04.050
DO - 10.1016/j.biomaterials.2013.04.050
M3 - Article
C2 - 23683723
AN - SCOPUS:84878114080
VL - 34
SP - 5958
EP - 5968
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 24
ER -