Ion-Pair-Enhanced Double-Click Driven Cell Adhesion and Altered Expression of Related Genes

• Published in: Bioconjugate chemistry Vol. 34; no. 4; pp. 638 - 644
• Main Authors: Kitagawa, Kohei, Okuma, Nao, Yoshinaga, Moeka, Takemae, Hitoshi, Sato, Fumiya, Sato, Shoma, Nakabayashi, Seiichiro, Yoshikawa, Hiroshi Y., Suganuma, Masami, Luedtke, Nathan, Matsuzaki, Takahisa, Tera, Masayuki
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 10.02.2023; Amer Chemical Soc
• Subjects: Adhesion; Biochemical Research Methods; Biochemistry & Molecular Biology; Cations; Cell adhesion; Cell interactions; Cell surface; Chemistry; Chemistry, Multidisciplinary; Chemistry, Organic; Crosslinking; Gene expression; Glass substrates; Ion pairs; Kinetics; Life Sciences & Biomedicine; Lung cancer; Physical Sciences; Proximity effect (electricity); Science & Technology; Substrates; CHEMISTRY; HYDROGELS; INTEGRINS; IMMOBILIZATION; SURFACES
• ISSN: 1043-1802; 1520-4812; 1520-4812
• DOI: 10.1021/acs.bioconjchem.2c00569

Bio-orthogonal ligations that crosslink living cells with a substrate or other cells require high stability and rapid kinetics to maintain the nature of target cells. In this study, we report water-soluble cyclooctadiyne (WS-CODY) derivatives that undergo an ion-pair enhanced double-click reaction. The cationic side chain of WS-CODY accelerated the kinetics on the azide-modified cell surface due to proximity effect. Cationic WS-CODY was able to crosslink azide-modified, poorly adherent human lung cancer PC-9 cells not only to azide-grafted glass substrates but also to other cells within 5–30 min. We discovered that cell–substrate crosslinking induced the ITGA5 gene expression, whereas cell–cell crosslinking induced the CTNNA1 gene, according to the adhesion partner. Ion-pair-enhanced WS-CODY can be applied to a wide range of cells with established azide modifications and is expected to provide a powerful tool to regulate cell–substrate and cell–cell interactions.