Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1. (26th January 2021)

• Record Type: Journal Article
• Authors: Bochicchio, Brigida; Yeo, Giselle C.; Lee, Pearl; Emul, Deniz; Pepe, Antonietta; Laezza, Antonio; Ciarfaglia, Nicola; Quaglino, Daniela; Weiss, Anthony S.
• Is Part Of: FEBS journal. Volume 288:Number 13(2021)
• Page Start: 4024
• Page End: 4038
• Publication Date: 2021-01-26
• Subjects: circular dichroism -- glycosaminoglycan -- heparan sulfate -- integrin -- lysine -- tropoelastin; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15702
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Elastin is an extracellular matrix component with key structural and biological roles in elastic tissues. Interactions between resident cells and tropoelastin, the monomer of elastin, underpin elastin's regulation of cellular processes. However, the nature of tropoelastin–cell interactions and the contributions of individual tropoelastin domains to these interactions are only partly elucidated. In this study, we identified and characterized novel cell‐adhesive sites in the tropoelastin N‐terminal region between domains 12 and 16. We found that this region interacts with αV and α5β1 integrin receptors, which mediate cell attachment and spreading. A peptide sequence from within this region, spanning domains 14 to mid‐domain 16, binds heparan sulfate through electrostatic interactions with peptide lysine residues and induces conformational ordering of the peptide. We propose that domains 14–16 direct initial cell attachment through cell‐surface heparan sulfate glycosaminoglycans, followed by αV and α5β1 integrin‐promoted attachment and spreading on domains 12–16 of tropoelastin. These findings advance our mechanistic understanding of elastin matrix biology, with the potential to enhance tissue regenerative outcomes of elastin‐based materials. Abstract : This paper identifies novel cell‐adhesive sites in domains 12–16 of human tropoelastin. The peptide 246–281 sequence within domains 14–16 directs initial cell contact by binding cell‐surface heparan sulfate via electrostatic interactions. This binding is followed by integrin‐promoted cell attachment and spreading on domains 12–16. These findings advance our mechanistic understanding of elastin matrix biology, with the potential to enhance the tissue regenerative outcomes of elastin‐based materials.