Morphological Transformation of Peptide Nanoassemblies through Conformational Transition of Core-forming Peptides

Abstract

Morphological control of nanostructures that are composed of amphiphilic di- or tri-block molecules by external stimuli broadens their applications for molecular containers, nanoreactors, and controlled release materials. In this study, triblock amphiphiles comprising oligo(ethylene glycol), oligo(l-lysine), and tetra(l-phenylalanine) were prepared for the construction of nanostructures that can transform accompanying α-to-β transition of core-forming peptides. Circular dichroic (CD) measurements showed that the triblock amphiphiles adopted different secondary structures depending on the solvent environment: they adopt β-sheet structures in aqueous solution, while α-helix structures in 25% 2,2,2-trifluoroethanol (TFE) solution under basic pH conditions. Transmission electron microscopic (TEM) observation revealed that the triblock amphiphiles formed vesicle structures in 25% TFE aq. Solvent exchange from 25% TFE to water induced morphological transformation from vesicles to arc-shaped nanostructures accompanying α-β conformational transition. The transformable nanostructures may be useful as novel smart nanomaterials for molecular containers and micro reactors.

Keywords: aromatic peptides; morphological change; secondary structure; self-assembly.

Figure 1

Circular dichroic (CD) spectra of K₂₀-EG₁₂ (a,b), K₁₆F₄-EG₁₂ (c,d), and F₄K₁₆-EG₁₂ (e,f). The measurements were performed in water (a,c,e) and in 25% 2,2,2-trifluoroethanol (TFE) aqueous solution (b,d,f) at various pHs at room temperature.

Figure 2

(a,b) Transmission electron microscopic (TEM) images of the nanostructures of F₄K₁₆-EG₁₂ obtained in 25% TFE aqueous solution at pH 9.6 (a) and at pH 8.9 (b). (c) TEM image of the nanostructures of K₂₀-EG₁₂ obtained in 25% TFE aqueous solution at pH 9.3. (d) TEM image of the nanostructures of K₁₆F₄-EG₁₂ obtained in 25% TFE aqueous solution at pH 9.7. (e) CD spectra of the nanostructures corresponding to (a) (blue), (c) (red), and (d) (green).

Figure 3

(a,b) TEM images of the nanostructures of F₄K₁₆-EG₁₂ obtained by the dialysis of its vesicle dispersion against buffer solution at pH 12.0 (a) and at pH 10.9 (b). (c) CD spectra of F₄K₁₆-EG₁₂ nanostructures obtained by solvent exchange at various pHs. (d) pH dependence of θ₂₁₇ for the F₄K₁₆-EG₁₂ nanostructures. (e) Schematic illustration of morphological transition of F₄K₁₆-EG₁₂ from vesicles to arc-shaped nanostructures or long nanofibers.