title: Light-activated hydrogel formation via the triggered folding and self-assembly of a designed peptide.
abstract: Photopolymerization can be used to construct materials with precise temporal and spatial resolution. Applications such as tissue engineering, drug delivery, the fabrication of microfluidic devices and the preparation of high-density cell arrays employ hydrogel materials that are often prepared by this technique. Current photopolymerization strategies used to prepare hydrogels employ photoinitiators, many of which are cytotoxic and require large macromolecular precursors that need to be functionalized with moieties capable of undergoing radical cross-linking reactions. We have developed a simple light-activated hydrogelation system that employs a designed peptide whose ability to self-assemble into hydrogel material is dependent on its intramolecular folded conformational state. An iterative design strategy afforded MAX7CNB, a photocaged peptide that, when dissolved in aqueous medium, remains unfolded and unable to self-assemble; a 2 wt % solution of freely soluble unfolded peptide is stable to ambient light and has the viscosity of water. Irradiation of the solution (260 < lambda < 360 nm) releases the photocage and triggers peptide folding to produce amphiphilic beta-hairpins that self-assemble into viscoelastic hydrogel material. Circular dichroic (CD) spectroscopy supports this folding and self-assembly mechanism, and oscillatory rheology shows that the resulting hydrogel is mechanically rigid (G' = 1000 Pa). Laser scanning confocal microscopy imaging of NIH 3T3 fibroblasts seeded onto the gel indicates that the gel surface is noncytotoxic, conducive to cell adhesion, and allows cell migration. Lastly, thymidine incorporation assays show that cells seeded onto decaged hydrogel proliferate at a rate equivalent to cells seeded onto a tissue culture-treated polystyrene control surface.
authors.affiliation: Department of Chemistry and Biochemistry and Materials Science and Engineering, Delaware Biotechnology Institute, University of Delaware, Newark, 19716-2522, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Haines
authors.forename: Karthikan
authors.initials: K
authors.lastname: Rajagopal
authors.forename: Bulent
authors.initials: B
authors.lastname: Ozbas
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Salick
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.forename: Joel P
authors.initials: JP
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D009994:Osmolar Concentration; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010777:Photochemistry; D017510:Protein Folding; D012212:Rheology
chemical_list: D020100:Hydrogels; D010455:Peptides