Rational design of charged peptides that self-assemble into robust nanofibers as immune-functional scaffolds. (June 2017)

• Record Type: Journal Article
• Authors: Zhang, Hangyu; Park, Jaehyung; Jiang, Yonghou; Woodrow, Kim A.
• Is Part Of: Acta biomaterialia. Volume 55(2017)
• Page Start: 183
• Page End: 193
• Publication Date: 2017-06
• Subjects: Self-assembly -- Peptide -- Nanofiber -- Hydrogel -- Scaffold; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2017.03.041
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Highlights: Self-assembling peptides are rationally designed for targeted properties. Designer peptides undergo salt-triggered self-assembly into nanofibers. Nanofibers are ultrastable in extreme pH (0–14) and dilute solutions (>5 μM). Robust hydrogels are formed upon salt-triggering in physiological conditions. Nanofibers carrying OVA257-264 enhance CD8 + T cell activation in vitro. 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 OVA257-264 peptide. Nanofibers carrying OVA257-264 significantly 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. Statement of Significance: 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.