(315g) Design and Function of Peptide-Based Materials

Fibrillar self-assembling peptide aggregates are abundant in nature and are used in various synthetic technologies in biomedical research and material science. The high level organization of the peptide aggregates emerges from small changes in the amino acid sequence that provides non-covalent interactions, such as electrostatic forces, hydrogen bonds, hydrophobic effects, and aromatic stacking. Discovery of peptide sequences that assemble into nanostructures with desired properties and functions in the proper context is a significant challenge for the field. Studies based on editing the peptide sequences of natural designs typically have an initial focus on a particular type of interaction for the property of interest, which may restrict the achievable material properties. As a result, there is a need for a strategy that can optimize the exploratory scope with the benefits of editing known sequences to map and search new peptides for new functionalities.

We addressed this need with a new molecular discovery tool. Rather than attempt a brute-force approach, we instead identify a new strategy for discovering and studying intermolecular interactions; “co-assembly of oppositely charged peptide" (CoOP), a framework that `encourages' peptide assembly by mixing two oppositely charged hexapeptides.1This results in a reasonable expansive design space of fibrillar assembly’s within that space leading to substantially increased efficiency in the exploration. The one-dimensional assemblies that form through this unique CoOP approach are well suited for study via a set of reliable quantitative tools. We showed that the peptides that are designed with CoOP strategy have wide application areas. The peptides that self-assemble into the fibrillar structures created hydrogels with different mechanical properties, based on their aggregation kinetics and affinity. Additionally, we showed the use of these peptides as vaccine adjuvants.2 We showed that the CoOP approach represents a unique, simple, and elegant framework that can be used to identify the structure-property relations of self-assembling peptide-based materials.

[1] Hamsici, S., White, A. D. & Acar, H. Science Advances (2022)

[2] Gunay, G.Hamsici, S., & Acar, H. BioRxiv (2022)