Tuning nanostructure dimensions with supramolecular twisting

Abstract

Peptide amphiphiles are molecules containing a peptide segment covalently bonded to a hydrophobic tail and are known to self-assemble in water into supramolecular nanostructures with shape diversity ranging from spheres to cylinders, twisted ribbons, belts, and tubes. Understanding the self-assembly mechanisms to control dimensions and shapes of the nanostructures remains a grand challenge. We report here on a systematic study of peptide amphiphiles containing valine-glutamic acid dimeric repeats known to promote self-assembly into belt-like flat assemblies. We find that the lateral growth of the assemblies can be controlled in the range of 100 nm down to 10 nm as the number of dimeric repeats is increased from two to six. Using circular dichroism, the degree of β-sheet twisting within the supramolecular assemblies was found to be directly proportional to the number of dimeric repeats in the PA molecule. Interestingly, as twisting increased, a threshold is reached where cylinders rather than flat assemblies become the dominant morphology. We also show that in the belt regime, the width of the nanostructures can be decreased by raising the pH to increase charge density and therefore electrostatic repulsion among glutamic acid residues. The control of size and shape of these nanostructures should affect their functions in biological signaling and drug delivery.

Figure 1

(A) Chemical structures of (VE)₂, (VE)₄, and (VE)₆. (B–D) Cryogenic transmission electron micrographs of (VE)₂, (VE)₄, and (VE)₆ nanostructures formed in 5 mM solutions of PA. Scalebars: 200 nm.

Figure 2

Scattering profiles of 5mM solutions of (VE)₂, (VE)₄, and (VE)₆ fitted with core-shell parallelepiped fits (solid red lines). Scattering intensities were adjusted for clarity.

Figure 3

(A–C) Atomic force microscopy images of dried films of 1 mM solutions of (VE)₂, (VE)₄, and (VE)₆.

Figure 4

(A) Circular dichroism of (VE)₂, (VE)₄, and (VE)₆ PAs. Inset shows the shift in minima for (VE)₄ and (VE)₆. (B) Red-shifting of PAs appears correlated with nanostructure width, as measured from cryo-TEM images. (C–E) Schematics of the proposed structures for (VE)₂, (VE)₄, and (VE)₆.

Figure 5

(A–C) Cryogenic transmission electron micrographs of 5 mM solutions of (VE)₂ PA at pH 7, 8, and 9. (D) Width distributions of (VE)₂ PA at varying pH, as measured by cryo-TEM images. (E) Circular dichroism of (VE)₂ PA at pH 7, 8, and 9.