title: Photodynamic control of bioactivity in a nanofiber matrix.
abstract: Self-assembling peptide materials have been used extensively to mimic natural extracellular matrices (ECMs) by presenting bioactive epitopes on a synthetic matrix. Although this approach can facilitate a desired response from cells grown in the matrix, it lacks the capacity for spatial or temporal regulation of the presented signals. We describe here a photoresponsive, synthetic ECM using a supramolecular platform composed of peptide amphiphiles (PAs) that self-assemble into cylindrical nanofibers. A photocleavable nitrobenzyl ester group was included in the peptide backbone using a novel Fmoc-amino acid that is compatible with microwave-assisted solid-phase peptide synthesis. The placement of the photolabile group on the peptide backbone enabled efficient removal of the ECM-derived cell adhesion epitope RGDS from PA molecules upon exposure to light (half-life of photolysis ~1.9 min) without affecting the nanofiber assembly. Fibroblasts cultured on RGDS-presenting PA nanofiber substrates demonstrated increased cell spreading and more mature focal adhesions compared with unfunctionalized and control (RGES-presenting) surfaces, as determined by immunostaining and cell morphological analysis. Furthermore, we observed an arrest in fibroblast spreading on substrates containing a cleavable RGDS epitope when the culture was exposed to light; in contrast, this dynamic shift in cell response was absent when the RGDS epitope was attached to the PA molecule by a light-insensitive control linker. Light-responsive bioactive materials can contribute to the development of synthetic systems that more closely mimic the dynamic nature of native ECM.
authors.affiliation: Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sur
authors.forename: John B
authors.initials: JB
authors.lastname: Matson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Newcomb
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000528:radiation effects; D005109:Extracellular Matrix / Q000378:metabolism* / Q000528:radiation effects*; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D016023:Integrins / Q000378:metabolism; D007700:Kinetics; D008027:Light; D057139:Nanofibers / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010782:Photolysis
chemical_list: D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid