Controlling lamination and directional growth of β-sheets via hydrophobic interactions: The strategies and insights

The self-assembling morphologies of proteins, nucleic acids, and peptides are well correlated with their functioning in biological systems. In spite of extensive studies for the morphologies regulating, the directional control of the assembly morphology structure for the peptides still remains challenging. Here, the directional structure control of a bola-like peptide Ac-KIIF-CONH₂ (KIIF) was realized by introducing different amount of acetonitrile to the system. The morphologies were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), and the secondary structure was evaluated by circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR). The results demonstrated that the introducing of different amount of acetonitrile has significantly tuned the hydrophobic interactions amongst the side chains, thus affecting the self-assembling morphologies. As acetonitrile content increased, the assemblies changed from nanotubes to helical/twisted ribbons and then to thin fibrils, with a steady decrease in the width. In contrast, the assemblies changed from thin fibrils to helical/twisted ribbons, and then to matured nanotubes, exhibiting a steady increase in the width with peptide concentration increasing. Complementary molecular dynamics (MD) simulations demonstrated the important role of acetonitrile in controlling the hydrophobic interactions, providing microscopic evidence for the structure transition process. We believe such observations provide important insights into the design and fabrication of functional materials with controlled shape and size.