Construction and Control of Self-Assembly of Amyloid and Fibrous Peptides

The aggregation of peptides and proteins into amyloid fibrils is most commonly associated with a variety of serious diseases such as Alzheimer’s disease and the transmissible spongiform encephalopathies (prion diseases). Amyloid-like fibrils are undesirable states for proteins as biomolecules, however, these are fascinating nanoconstructs because of their highly ordered tertiary structure in which numerous β-stranded polypeptide chains align regularly. These kinds of fibrous peptides have the potential to be engineered into ones revealing basic insights into amyloid formation and protein folding, as well as developing novel peptidyl nanoscale materials. We have demonstrated that de novo designed peptides undergo self-initiated structural transition and fibril formation, showing representative properties of amyloid. Cofibril formation from two, three, or four peptide species with well-designed amino acid sequences was achieved, so that the charged residues within the β-strands were complementary to each other. This homologous recognition mechanism can be applied for the inhibition of the fibril formation. Meanwhile, cofibril formation indicates a possibility of functionalizing the fibrils by co-assembling of peptides with various elements to develop a fibrous peptide material as a well-ordered nanoconstruct. Another designing approach demonstrated the production of unique straight nanofibers with defined widths. The fibrils may make a nanoscaffold onto which a variety of functional groups can be arranged. The studies on engineering fibrous peptides will afford insight into desease-related amyloid formation and will help to develop nanoscale fibrous constructs.