Peptide Self-Assembled Nanostructures with Distinct Morphologies and Properties Fabricated by Molecular Design

Six surfactant-like peptides with the same amino acid composition but different primary sequences are designed, including G₃A₃V₃I₃K₃, K₃I₃V₃A₃G₃, I₃V₃A₃G₃K₃, K₃G₃A₃V₃I₃, V₃G₃I₃A₃K₃, and K₃A₃I₃G₃V₃. These peptides form antiparallel β-sheets during self-assembly. Because the constituent residues have different side chain size and hydrophobicity, sequence changes adjust group distribution and hydrophobicity on the two sides of a given β-sheet. This consequently tunes the binding energy of the side-to-side pairing conformations and leads to different self-assembled structures. G₃A₃V₃I₃K₃ and K₃I₃V₃A₃G₃ form short nanorods with diameters of 8.5 ± 1.0 nm and lengths <150 nm. I₃V₃A₃G₃K₃ and K₃G₃A₃V₃I₃ form nanosheets with heights of 4.0 ± 0.5 nm and limited lengths and widths. V₃G₃I₃A₃K₃ and K₃A₃I₃G₃V₃ form long fibrils with diameters of 7.0 ± 1.0 nm and lengths of micrometer scale. These nanostructures exhibit different capacity in encapsulating insoluble hydrophobic drug molecules and delivering them into the cells. The nanosheets of I₃V₃A₃G₃K₃ and K₃G₃A₃V₃I₃ can encapsulate both nile red and doxorubicin molecules to an extent of up to 17-23% in mole ratio. Moreover, the shape and size of the nanostructures affect the drug delivery into cells greatly, with the nanosheets and short rods exhibiting higher efficiency than the long fibrils. The study provides new insights into programmed peptide self-assembly toward specific functionalities.