title: Rational design of charged peptides that self-assemble into robust nanofibers as immune-functional scaffolds.
abstract: Self-assembling peptides programed by sequence design to form predefined nanostructures are useful for a variety of biomedical applications. However, assemblies of classic ionic self-complementary peptides are unstable in neutral pH, while charged peptide hydrogels have low mechanical strength. Here, we report on the rational design of a self-assembling peptide system with optimized charge distribution and density for bioscaffold development. Our designer peptides employs a sequence pattern that undergoes salt triggered self-assembly into β-sheet rich cationic nanofibers in the full pH range (pH 0-14). Our peptides form nanofibrils in physiological condition at a minimum concentration that is significantly lower than has been reported for self-assembly of comparable peptides. The robust fiber-forming ability of our peptides results in the rapid formation of hydrogels in physiological conditions with strong mechanical strength. Moreover, fiber structure is maintained even upon dense conjugation with a model bioactive cargo OVA257-264peptide. Nanofibers carrying OVA257-264significantly enhanced CD8+T cell activation in vitro. Subcutaneous immunization of our peptide fiber vaccine also elicited robust CD8+T cell activation and proliferation in vivo. Our self-assembling peptides are expected to provide a versatile platform to construct diverse biomaterials.
  
  
  
  This work is an attempt of rational design of materials from molecular level for targeted properties and an exploration in molecular self-assembly. Current widely studied self-assembling peptides do not have stable nanofiber structures and form weak hydrogels under physiological conditions. To address this issue, we develop charged self-assembling peptides with a novel sequence pattern for strong fiber-forming ability under physiological conditions. Our designer peptides can undergo salt-triggered self-assembly into nanofibers that are ultrastable in extreme pH (0-14) and dilute solutions, and into hydrogels with strong mechanical strength. Upon conjugation with a model bioactive cargo, our self-assembled peptides exhibit great potential as bioscaffolds for multiple applications.
authors.affiliation: Department of Bioengineering, University of Washington, Foege N410D, 3720 15th Ave NE, Seattle, WA 98195-5061, USA.
authors.forename: Hangyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of Washington, Foege N410D, 3720 15th Ave NE, Seattle, WA 98195-5061, USA.
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Bioengineering, University of Washington, Foege N410D, 3720 15th Ave NE, Seattle, WA 98195-5061, USA.
authors.forename: Yonghou
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Bioengineering, University of Washington, Foege N410D, 3720 15th Ave NE, Seattle, WA 98195-5061, USA. Electronic address: woodrow@uw.edu.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Woodrow
mesh_terms: D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057139:Nanofibers / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels; D010455:Peptides
keywords: Hydrogel; Nanofiber; Peptide; Scaffold; Self-assembly