(159a) Understanding Amyloid Co-Assembly Bycharge-Complementary Peptides

Peptide self-assembly has long been recognized as a key technology for preparing nanomaterials with desired structures and functions for medical and biotechnology applications. Recently, co-assembly of peptides with complementary partial charges has emerged as a new platform for preparing peptide-based nanomaterials. Two different peptides co-assemble into fibrils rich in β-sheet when mixed together but remain random coils when by themselves. It has been hypothesized that peptides with opposite partial charges adopt an alternating arrangement in the fibril, but there is no direct evidence at the molecular level to support this hypothesis. We investigate the co-assembly of three charge-complementary peptide systems: CATCH46 (QQKFKFKFKQQ and EQEFEFEFQE), CATCH44 (KQKFKFKFKQK and EQEFEFEFQE), and CATCH66 (KQKFKFKFKQK and EQEFEFEFQE) using molecular modeling, solid state NMR and standard biophysical measurements. Both simulation and solid-state NMR support the alternating peptide hypothesis but show exceptions in which peptides with the same charge are adjacent to each other. Molecular modeling further shows that the peptides can co-assemble into a β-barrel structure; the role of this oligomer in the co-assembly processes is discussed.