Molecular self-assembly of peptide nanostructures: mechanism of association and potential uses

Molecular self-assembly offers unique directions for the fabrication of novel supramolecular structures and advanced materials. The inspiration for the development of such structures is often derived from self-assembling modules in biology, as natural systems form complex structures from simple building blocks such as amino acids, nucleic acids and lipids. Peptide-based nanostructures indicate an important route toward the production of ordered nanostructures as several studies had demonstrated their ability to form well organized assemblies. This includes cyclic peptides designed with alternating D- and L-amino acids, amphiphile peptides, peptide-conjugates and ionic self-complementary peptides. A naturally occurring self-assembly process of nano scale objects by polypeptides is that of amyloid fibril formation. These 7-10 nm fibrillar assemblies were already used for the formation of conductive nanowires. Short peptides have been used as model systems to study the molecular mechanism that leads to amyloid fibril formation. Based on the analysis of short amyloid fort-ning fragments, it was recently suggested by our group and others that aromatic interactions may play a significant role in the process of amyloid fibrils formation in several cases. This hypothesis led to the discovery that the core recognition motif of the Alzheimer's beta-amyloid polypeptide, the diphenylalanine element, has all the molecular information needed to self assemble into a novel class of peptide nanotubes. A highly similar analog and the simplest aromatic dipeptide, the diphenylglycine, forms spherical nanometric assemblies. Both designed and peptide fragment nanostructures were suggested to have many applications in various fields including molecular electronics, tissue engineering, and material science.