“All-in-one” in vitro selection of collagen-binding vascular endothelial growth factor

Shin Hye Park, Takanori Uzawa, Fumiyuki Hattori, Shuichi Ogino, Naoki Morimoto, Satoshi Tsuneda, Yoshihiro Ito

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    To enhance the therapeutic effect of growth factors, a powerful strategy is to direct their localization to damaged sites. To treat skin wounds and myocardial infarction, we selected vascular endothelial growth factor (VEGF) carrying binding affinity to collagen. A simple conjugation of a reported collagen-binding sequence and VEGF did not increase the collagen-binding affinity, indicating that the molecular interaction between the two proteins abolished collagen binding activity. Here, we present a new molecular evolution strategy, “all-in-one” in vitro selection, in which a collagen-binding VEGF (CB-VEGF) was directly identified from a random library consisting of random and VEGF sequences. As expected, the selected CB-VEGFs exhibited high binding affinity to collagen and maintained the same growth enhancement activity for endothelial cells as unmodified VEGF in solution. Furthermore, the selected CB-VEGF enhanced angiogenesis at skin wounds and infarcted myocardium. This study demonstrates that “all-in-one” in vitro selection is a novel strategy for the design of functional proteins for regenerative medicine.

    Original languageEnglish
    Pages (from-to)270-278
    Number of pages9
    JournalBiomaterials
    Volume161
    DOIs
    Publication statusPublished - 2018 Apr 1

    Fingerprint

    Collagen
    Vascular Endothelial Growth Factor A
    Skin
    Vascular Endothelial Growth Factors
    Proteins
    Regenerative Medicine
    Molecular Evolution
    Molecular interactions
    Endothelial cells
    Wounds and Injuries
    Therapeutic Uses
    In Vitro Techniques
    Intercellular Signaling Peptides and Proteins
    Libraries
    Myocardium
    Endothelial Cells
    Myocardial Infarction
    Growth

    Keywords

    • Binding affinity
    • Collagen
    • In vitro selection
    • Vascular endothelial growth factor

    ASJC Scopus subject areas

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

    Cite this

    “All-in-one” in vitro selection of collagen-binding vascular endothelial growth factor. / Park, Shin Hye; Uzawa, Takanori; Hattori, Fumiyuki; Ogino, Shuichi; Morimoto, Naoki; Tsuneda, Satoshi; Ito, Yoshihiro.

    In: Biomaterials, Vol. 161, 01.04.2018, p. 270-278.

    Research output: Contribution to journalArticle

    Park, Shin Hye ; Uzawa, Takanori ; Hattori, Fumiyuki ; Ogino, Shuichi ; Morimoto, Naoki ; Tsuneda, Satoshi ; Ito, Yoshihiro. / “All-in-one” in vitro selection of collagen-binding vascular endothelial growth factor. In: Biomaterials. 2018 ; Vol. 161. pp. 270-278.
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    AU - Morimoto, Naoki

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