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

UNLABELLED

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 OVA peptide. Nanofibers carrying OVA 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.