Small-Molecule-Induced Clustering of Heparan Sulfate Promotes Cell Adhesion

Takemoto, Naohiro; Suehara, Tetsuya; Frisco, Heidie L.; Sato, Shin-ichi; Sezaki, Takuhito; Kusamori, Kosuke; Kawazoe, Yoshinori; Min Park, Sun; Yamazoe, Sayumi; Mizuhata, Yoshiyuki; Inoue, Rintaro; Miller, Gavin J.; Hansen, Steen U.; Jayson∥, Gordon C.; Gardiner, John M.; Kanaya, Toshiji; Tokitoh, Norihiro; Ueda, Kazumitsu; Takakura, Yoshinobu; Kioka, Noriyuki; Nishikawa, Makiya; Uesugi, Motonari

doi:10.1021/ja4018682

Small-Molecule-Induced Clustering of Heparan Sulfate Promotes Cell Adhesion

Takemoto, Naohiro; Suehara, Tetsuya; Frisco, Heidie L.; Sato, Shin-ichi; Sezaki, Takuhito; Kusamori, Kosuke; Kawazoe, Yoshinori; Min Park, Sun; Yamazoe, Sayumi; Mizuhata, Yoshiyuki; Inoue, Rintaro; Miller, Gavin J.; Hansen, Steen U.; Jayson∥, Gordon C.; Gardiner, John M.; Kanaya, Toshiji; Tokitoh, Norihiro; Ueda, Kazumitsu; Takakura, Yoshinobu; Kioka, Noriyuki; Nishikawa, Makiya; Uesugi, Motonari

Authors

Naohiro Takemoto

Tetsuya Suehara

Heidie L. Frisco

Shin-ichi Sato

Takuhito Sezaki

Kosuke Kusamori

Yoshinori Kawazoe

Sun Min Park

Sayumi Yamazoe

Yoshiyuki Mizuhata

Rintaro Inoue

Gavin Miller g.j.miller@keele.ac.uk

Steen U. Hansen

Gordon C. Jayson∥

John M. Gardiner

Toshiji Kanaya

Norihiro Tokitoh

Kazumitsu Ueda

Yoshinobu Takakura

Noriyuki Kioka

Makiya Nishikawa

Motonari Uesugi

Abstract

Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy.

Citation

Takemoto, N., Suehara, T., Frisco, H. L., Sato, S., Sezaki, T., Kusamori, K., …Uesugi, M. (2013). Small-Molecule-Induced Clustering of Heparan Sulfate Promotes Cell Adhesion. Journal of the American Chemical Society, 135(30), 11032 -11039. https://doi.org/10.1021/ja4018682

Journal Article Type	Article
Acceptance Date	Jul 3, 2013
Online Publication Date	Jul 17, 2013
Publication Date	Jul 31, 2013
Journal	Journal Of The American Chemical Society
Print ISSN	0002-7863
Publisher	American Chemical Society
Peer Reviewed	Peer Reviewed
Volume	135
Issue	30
Pages	11032 -11039
DOI	https://doi.org/10.1021/ja4018682
Publisher URL	http://dx.doi.org/10.1021/ja4018682