Self-Assembled Amyloid Peptides with Arg-Gly-Asp (RGD) Motifs As Scaffolds for Tissue Engineering.
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Self-assembled peptides gain increasing interest as biocompatible and biodegradable scaffolds for tissue engineering. Rationally designed self-assembling building blocks that carry cell adhesion motifs such as Arg-Gly-Asp (RGD) are especially attractive. We have used a combination of theoretical and experimental approaches toward such rational designs, especially focusing on modular designs that consist of a central ultrashort amphiphilic motif derived from the adenovirus fiber shaft. In this study, we rationally designed RGDSGAITIGC, a bifunctional self-assembling amyloid peptide which encompasses cell adhesion and potential cysteine-mediated functionalization properties through the incorporation of an RGD sequence motif and a cysteine residue at the N- and C- terminal end, respectively. We performed replica exchange MD simulations that suggested that the key factor determining cell adhesion is the total solvent accessibility of the RGD motif and also that the C-terminal cysteine is adequately exposed. The designer peptides self-assembled into fibers that are structurally characterized with Transmission Electron Microscopy, Scanning Electron Microscopy and X-ray fiber diffraction. Furthermore, they supported cell adhesion and proliferation of a model cell line. We consider that the current bifunctional properties of the RGDSGAITIGC fibril-forming peptide can be exploited to fabricate novel biomaterials with promising biomedical applications. Such short self-assembling peptides that are amenable to computational design offer open-ended possibilities toward multifunctional tissue engineering scaffolds of the future.
author list (cited authors)
Deidda, G., Jonnalagadda, S., Spies, J. W., Ranella, A., Mossou, E., Forsyth, V. T., ... Mitraki, A
complete list of authors
Deidda, Graziano||Jonnalagadda, Sai Vamshi R||Spies, Jacob W||Ranella, Anthi||Mossou, Estelle||Forsyth, V Trevor||Mitchell, Edward P||Bowler, Matthew W||Tamamis, Phanourios||Mitraki, Anna