(283g) Uncovering Sequence-Structure Relationships for Engineering Coassembled Peptide Nanofibers | AIChE

(283g) Uncovering Sequence-Structure Relationships for Engineering Coassembled Peptide Nanofibers


Paravastu, A., Georgia Institute of Technology
Wang, Y., University of Pennsylvania
Seroski, D. T., University of Florida
Liu, R., University of Florida
Shao, Q., Nanjing University of Technology
Xiao, X., North Carolina State University
Hudalla, G., University of Wisconsin
Peptide coassembly expands the design space of tunable peptide-based functional biomaterials for applications such as tissue engineering, drug delivery, and photoactive material design. Peptide coassembly occurs when two distinct peptide sequences A and B are engineered to spontaneously co-organize into nanofibers in solution. Many coassembling peptide pairs rely on complementary electrostatic interactions between positively charged peptide A and negatively charged peptide B to confer coassembly behavior. As a result, these coassembling pairs were originally thought to arrange into ideal coassembled antiparallel β-sheets with perfect alternation of peptides A and B. However, our solid-state NMR measurements and computational simulations on two existing coassembling systems, King-Webb peptides and CATCH peptides, revealed significant deviations from the ideal nanofiber structure. These deviations highlight a knowledge gap in the sequence-structure relationships underpinning peptide coassembly. In recent studies, we have altered the peptide’s net charge and the charged residue sidechain group to generate CATCH peptide variants. The coassembled β-sheet nanostructure and fiber morphology differed systematically with peptide charge as observed by solid-state NMR and TEM measurements. In another approach, we designed a computational screening algorithm to identify new coassembling peptide pairs. Analysis of 1D 13C spectra of each newly identified pair suggest that these new sequences form more highly ordered and more stoichiometrically even (peptide A: peptide B) nanofibers than previous human-designed pairs. Analysis of the computationally derived sequences point towards design rules that promote coassembled antiparallel β-sheet nanofibers. Through our solid-state NMR measurements and computational simulations, we have begun to identify sequence design rules which manipulate nanofiber structure and fiber morphology. An understanding of the sequence-to-structure relationships underpinning binary peptide systems will allow us to finely control coassembled peptide nanofiber structure and properties for desired applications.