Heparin-functionalized thermoresponsive surface

A versatile cell culture substrate for regulating multivalent affinity binding with heparin-binding proteins by temperature changes

Yoshinori Arisaka, Jun Kobayashi, Masayuki Yamato, Yoshikatsu Akiyama, Teruo Okano

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Temperature-dependent regulation of affinity binding between bioactive ligands and their cell membrane receptors is an attractive approach for the dynamic control of cellular adhesion, proliferation, migration, differentiation, and signal transduction. Covalent conjugation of bioactive ligands onto thermoresponsive poly(N-isopropylacrylamide) (PIPAAm)-grafted surfaces facilitates the modulation of one-on-one affinity binding between bioactive ligands and cellular receptors by changing temperature. For the dynamic control of the multivalent affinity binding between heparin and heparin-binding proteins, thermoresponsive cell culture surface modified with heparin, which interacts with heparin-binding proteins such as basic fibroblast growth factor (bFGF), has been proposed. Heparin-functionalized thermoresponsive cell culture surface induces (1) the multivalent affinity binding of bFGF in active form and (2) accelerating cell sheet formation in the state of shrunken PIPAAm chains at 37°C. By lowering temperature to 20°C, the affinity binding between bFGF and immobilized heparin is reduced with increasing the mobility of heparin and the swollen PIPAAm chains, leading to the detachment of cultured cells. Therefore, heparin-functionalized thermoresponsive cell culture surface was able to enhance cell proliferation and detach confluent cells as a contiguous cell sheet by changing temperature. A cell cultivation system using heparin-functionalized thermoresponsive cell culture surface is versatile for immobilizing other heparin-binding proteins such as vascular endothelial growth factor, fibronectin, antithrombin III, and hepatocyte growth factor, etc. for tuning the adhesion, growth, and dif-ferentiation of various cell species.

    Original languageEnglish
    Pages (from-to)191-193
    Number of pages3
    JournalOrganogenesis
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 2013 Jul

    Fingerprint

    Cell culture
    Heparin
    Cell Culture Techniques
    Temperature
    Substrates
    Fibroblast Growth Factor 2
    Fibroblasts
    Ligands
    Cell Proliferation
    Hepatocyte Growth Factor
    Antithrombin III
    Adhesion
    human cationic antimicrobial protein CAP 37
    Carrier Proteins
    Fibronectins
    Vascular Endothelial Growth Factor A
    Signal transduction
    Cultured Cells
    Signal Transduction
    Cell proliferation

    Keywords

    • 2-carboxyisopropylacrylamide
    • Basic fibroblast growth factor
    • Cell sheet
    • Heparin
    • Poly(N-isopropylacrylamide)
    • Thermoresponsive cell culture surface

    ASJC Scopus subject areas

    • Developmental Biology
    • Embryology
    • Transplantation
    • Biomedical Engineering

    Cite this

    Heparin-functionalized thermoresponsive surface : A versatile cell culture substrate for regulating multivalent affinity binding with heparin-binding proteins by temperature changes. / Arisaka, Yoshinori; Kobayashi, Jun; Yamato, Masayuki; Akiyama, Yoshikatsu; Okano, Teruo.

    In: Organogenesis, Vol. 9, No. 3, 07.2013, p. 191-193.

    Research output: Contribution to journalArticle

    Arisaka, Yoshinori ; Kobayashi, Jun ; Yamato, Masayuki ; Akiyama, Yoshikatsu ; Okano, Teruo. / Heparin-functionalized thermoresponsive surface : A versatile cell culture substrate for regulating multivalent affinity binding with heparin-binding proteins by temperature changes. In: Organogenesis. 2013 ; Vol. 9, No. 3. pp. 191-193.
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