The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain

Mikaël M. Martino, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

It has recently been shown that some growth factors (GFs) have strong interactions with nonproteoglycan extracellular matrix proteins. Relevant here, the 12th-14th type three repeats of fibronectin (FN III12-14) have been shown to bind insulin-like growth factor binding-protein-3, fibroblast growth factor (FGF)-2, and vascular endothelial growth factor (VEGF)-A with high affinity. Since FN III12-14 is known to bind GFs from different families, we hypothesized that this domain could be highly promiscuous in its GF-binding capacity. We used biochemical approaches and surface plasmon resonance to investigate such interactions with recombinant FN III12-14. We found that FN III12-14 binds most of the GFs from the platelet-derived growth factor (PDGF)/VEGF and FGF families and some GFs from the transforming growth factor-β and neurotrophin families, with KD values in the nanomolar range, without inhibiting GF activity. Overall, 25 new binding interactions were identified. In a clinically relevant fibrin matrix, a fibrin-binding variant of FN III12-14 was highly effective as a GF delivery system. For instance, in matrices functionalized with FN III12-14, PDGF-BB-induced sprouting of human smooth muscle cell spheroids was greatly enhanced. We show that FN III12-14 is a highly promiscuous ligand for GFs and also holds great potential in clinical healing applications.

Original languageEnglish
Pages (from-to)4711-4721
Number of pages11
JournalFASEB Journal
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Fibronectins
Intercellular Signaling Peptides and Proteins
Fibrin
Vascular Endothelial Growth Factor A
Insulin-Like Growth Factor Binding Protein 3
Fibroblast Growth Factors
Extracellular Matrix Proteins
Platelet-Derived Growth Factor
Nerve Growth Factors
Surface plasmon resonance
Transforming Growth Factors
Fibroblast Growth Factor 2
Surface Plasmon Resonance
Muscle
Cells
Ligands
Smooth Muscle Myocytes

Keywords

  • Extracellular matrix
  • Heparin-binding domain
  • Tissue engineering

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. / Martino, Mikaël M.; Hubbell, Jeffrey A.

In: FASEB Journal, Vol. 24, No. 12, 01.12.2010, p. 4711-4721.

Research output: Contribution to journalArticle

Martino, Mikaël M. ; Hubbell, Jeffrey A. / The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. In: FASEB Journal. 2010 ; Vol. 24, No. 12. pp. 4711-4721.
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