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Collagen type IV-specific tripeptides for selective adhesion of endothelial and smooth muscle cells

Authors

  • Kei Kanie,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
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  • Yuji Narita,

    1. Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
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  • Yingzi Zhao,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
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  • Fumiaki Kuwabara,

    1. Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
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  • Makoto Satake,

    1. Integrative Technology Research Institute, Teijin Limited, Hino, Tokyo, Japan
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  • Susumu Honda,

    1. Integrative Technology Research Institute, Teijin Limited, Hino, Tokyo, Japan
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  • Hiroaki Kaneko,

    1. Integrative Technology Research Institute, Teijin Limited, Hino, Tokyo, Japan
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  • Tomohiko Yoshioka,

    1. Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Meguro-ku, Tokyo, 152-8550, Japan
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  • Mina Okochi,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
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  • Hiroyuki Honda,

    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
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  • Ryuji Kato

    Corresponding author
    1. Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
    • Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan; telephone: +81-52-789-3216; fax: 81-52-789-3214
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  • The authors declare no competing interests.

Abstract

Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) in blood vessels is critically important to minimize the risk associated with vascular implants. Extracellular matrix (ECM) plays a key role in controlling the cellular balance, suggesting a promising source of cell-selective peptides. To obtain EC- or SMC-selective peptides, we start by highlighting sequence differences found among ECM molecules as enriched targets for cell-selective peptides. We explored the EC- or SMC-selective performance of tripeptides that are specifically enriched only in collagen type IV, but not in types I, II, III, and V. Collagen type IV was chosen since it is the major ECM in the basement membrane of blood vessels, which separates ECs and SMCs. Among 114 collagen type IV-derived tripeptides pre-screened from in silico analysis, 22 peptides (19%) were found to promote cell-selective adhesion, as determined by peptide array. One of the best performing EC-selective peptides (Cys-Ala-Gly (CAG)) was mixed into an electrospun fine-fiber, a vascular graft material, for practical application. Compared to unmodified fiber, the CAG containing fiber surface was found to enhance adhesion of ECs (+190%) while limiting SMCs (−20%). These results are not only consistent with the hypothesis of ECM as a source of cell selective peptides, but also suggest a new genre of EC- or SMC-selective peptides for tissue engineering applications. Collectively, these findings favorably support the screening approach used to discover new peptides for these purposes. Biotechnol. Bioeng. 2012; 109:1808–1816. © 2012 Wiley Periodicals, Inc.

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