Octa-arginine and Octa-lysine Promote Cell Adhesion through Heparan Sulfate Proteoglycans and Integrins

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 2; pp. 207 - 212
• Main Authors: Yamada, Yuji, Onda, Toru, Hamada, Keisuke, Kikkawa, Yamato, Nomizu, Motoyoshi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.02.2022; Japan Science and Technology Agency
• Subjects: Actins - physiology; Biomaterials; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; cell attachment; Cell Proliferation; Cell spreading; Edetic Acid - pharmacology; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - physiology; Focal Adhesions - drug effects; Focal Adhesions - physiology; Heparan sulfate; heparan sulfate proteoglycan; Heparan sulfate proteoglycans; Heparan Sulfate Proteoglycans - metabolism; Heparin - pharmacology; Humans; integrin; Integrins; Integrins - metabolism; Lysine; Lysine - chemistry; Lysine - pharmacology; octa-arginine; octa-lysine; Oligopeptides - pharmacology; Peptides; Proteoglycans; Syndecan; cell spreading; cell attachment; octa-lysine; octa-arginine; heparan sulfate proteoglycan; integrin
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00791

Octa-arginine (R8) has been extensively studied as a cell-penetrating peptide. R8 binds to diverse transmembrane heparan sulfate proteoglycans (HSPGs), including syndecans, and is internalized by cells. R8 is also reported to bind to integrin β1. In this study, we evaluated the biological activities of R8 and octa-lysine (K8), a peptide similar to R8, with a focus on cell adhesion. R8 and K8 were immobilized on aldehyde-agarose matrices via covalent conjugation, and the effect of these peptides on cell attachment, spreading, and proliferation was examined using human dermal fibroblasts. The results indicated that R8- and K8-matrices mediate cell adhesion mainly via HSPGs. Moreover, R8- and K8-matrices interacted with integrin β1 and promote cell spreading and proliferation. These results are useful for further understanding of the R8-membrane interactions and the cellular uptake mechanisms. In addition, the R8- and K8-matrices may potentially be used as a multi-functional biomaterial to promote cell adhesion, spreading, and proliferation.