Capacity for increased surface area in the hydrophobic core of β-sheet peptide bilayer nanoribbons

Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self-assemble into beta-sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self-assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac-(XKXE)(2)-NH2 peptides (X = hydrophobic residue). A series of Ac-(XKXE)(2)-NH2 peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1-naphthylalanine [1-Nal], 2-naphthylalanine [2-Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self-assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac-X1KFEFKFE-NH2 and Ac-(X1,5KFE)-NH2 peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy indicated beta-sheet formation for all variants. Self-assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self-assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac-(XKXE)(2)-NH2 peptides correlates to self-assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self-assembled amphipathic peptides as functional biomaterials.

Automated summary

This study explores the self-assembly of amphipathic peptides with alternating patterns of hydrophobic and hydrophilic residues into beta-sheet bilayer nanoribbons. Increasing the surface area of aromatic side chain groups in the hydrophobic core did not affect self-assembly rates, while varying amino acids in the hydrophobic core resulted in morphological changes in the nanoribbon structures. The findings suggest that peptide hydrophobicity influences self-assembly propensity and the ability of the nanoribbon bilayers to accommodate steric functional groups.