Sequence-Dependent Bioactivity and Self-Assembling Properties of RGD-Containing Amphiphilic Peptides as Extracellular Scaffolds.

Abstract

Cell adhesion is a fundamental biological process involved in a wide range of cellular and biological activity. Integrin-ligand binding is largely responsible for cell adhesion with an extracellular matrix, and the RGD sequence is an epitope in ligand proteins such as fibronectin. The extracellular matrix consists of fibrous proteins with embedded ligands for integrins. Such a biological architecture has been reconstructed for biochemical, pharmaceutical, and biomaterial studies using artificial supramolecular systems to reproduce cell adhesion functionality, and fiber-forming self-assembling peptides containing RGD are one such promising material for this purpose. In this study, using RADA16 as a model fiber-forming peptide, a series of RGD-containing variants have been synthesized by the replacement of one alanine with glycine at different positions, in which all the variants consist of identical amino acid components. The position of the RGD unit influenced the supramolecular self-assembly of the amphiphilic peptide to inhibit β-sheet formation (A6G) or twist the molecular alignment in β-sheet-type assemblies (A10G and A14G). Furthermore, A10G and A14G formed assembled nanofibers, which afforded hydrogels with higher viscoelasticities than other RGD-containing variants. In contrast to A10G and A14G, which exhibit substantial cell adhesion functionality, the cell adhesion efficiencies of the other RGD-containing variants were significantly reduced. This suggests that the higher order structure could strongly influence the cell adhesion functionality of RGD-containing supramolecular nanofibers.