Molecular complementarity and structural heterogeneity within co-assembled peptide beta-sheet nanofibers

摘要

Self-assembling peptides have garnered an increasing amount of interest as a functional biomaterial for medical and biotechnological applications. Recently, beta-sheet peptide designs utilizing complementary pairs of peptides composed of charged amino acids positioned to impart co-assembly behavior have expanded the portfolio of peptide aggregate structures. Structural characterization of these charge-complementary peptide co-assemblies has been limited. Thus, it is not known how the complementary peptides organize on the molecular level. Through a combination of solid-state NMR measurements and discontinuous molecular dynamics simulations, we investigate the molecular organization of King-Webb peptide nanofibers. KW+ and KW- peptides co-assemble into near stoichiometric two-component beta-sheet structures as observed by computational simulations and C-13-C-13 dipolar couplings. A majority of beta-strands are aligned with antiparallel nearest neighbors within the beta-sheet as previously suggested by Fourier transform infrared spectroscopy measurements. Surprisingly, however, a significant proportion of beta-strand neighbors are parallel. While charge-complementary peptides were previously assumed to organize in an ideal (AB)(n) pattern, dipolar recoupling measurements on isotopically diluted nanofiber samples reveal a non-negligible amount of self-associated (AA and BB) pairs. Furthermore, computational simulations predict these different structures can coexist within the same nanofiber. Our results highlight structural disorder at the molecular level in a charge-complementary peptide system with implications on co-assembling peptide designs.