title: Cross-Linking Approaches to Tuning the Mechanical Properties of Peptide π-Electron Hydrogels.
abstract: Self-assembling peptides are extensively exploited as bioactive materials in applications such as regenerative medicine and drug delivery despite the fact that their relatively weak noncovalent interactions often render them susceptible to mechanical destruction and solvent erosion. Herein, we describe how covalent cross-linking enhances the mechanical stability of self-assembling π-conjugated peptide hydrogels. We designed short peptide-chromophore-peptide sequences displaying different reactive functional groups that can form cross-links with appropriately modified bifunctional polyethylene glycol (PEG)-based small guest molecules. These peptides self-assemble into one-dimensional fibrillar networks in response to pH in the aqueous environment. The cross-linking reactions were promoted to create a secondary network locked in place by covalent bonds within the physically cross-linked (preassembled) π-conjugated peptide strands. Rheology measurements were used to evaluate the mechanical modifications of the network, and the chemical changes that accompany the cross-linking were further confirmed by infrared spectroscopy. Furthermore, we modified these cross-linkable π-conjugates by incorporating extracellular matrix (ECM)-derived Ile-Lys-Val-Ala-Val (IKVAV) and Arg-Gly-Asp (RGD) bioactive epitopes to support human neural stem and progenitor cell (hNSCs) differentiation. The hNSCs undergo differentiation into neurons on IKVAV-derived π-conjugates while RGD-containing peptides failed to support cell attachment. These findings provide significant insight into the biochemical and electronic properties of π-conjugated peptide hydrogelators for creating artificial ECM to enable advanced tissue-engineering applications.
authors.forename: Wathsala
authors.initials: W
authors.lastname: Liyanage
authors.forename: Herdeline Ann M
authors.initials: HA
authors.lastname: Ardoña
authors.affiliation: Translational Tissue Engineering Center, Johns Hopkins School of Medicine , 400 North Broadway, Baltimore, Maryland 21287, United States.
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
authors.forename: John D
authors.identifier: 0000-0002-9650-2210
authors.initials: JD
authors.lastname: Tovar
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004583:Electrons; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007797:Laminin / Q000737:chemistry*; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012212:Rheology; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D007797:Laminin; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; C083321:isoleucyl-lysyl-valyl-alanyl-valine; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid