Ultrasmall peptides self-assemble into diverse nanostructures: morphological evaluation and potential implications

Abstract

In this study, we perform a morphological evaluation of the diverse nanostructures formed by varying concentration and amino acid sequence of a unique class of ultrasmall self-assembling peptides. We modified these peptides by replacing the aliphatic amino acid at the C-aliphatic terminus with different aromatic amino acids. We tracked the effect of introducing aromatic residues on self-assembly and morphology of resulting nanostructures. Whereas aliphatic peptides formed long, helical fibers that entangle into meshes and entrap >99.9% water, the modified peptides contrastingly formed short, straight fibers with a flat morphology. No helical fibers were observed for the modified peptides. For the aliphatic peptides at low concentrations, different supramolecular assemblies such as hollow nanospheres and membrane blebs were found. Since the ultrasmall peptides are made of simple, aliphatic amino acids, considered to have existed in the primordial soup, study of these supramolecular assemblies could be relevant to understanding chemical evolution leading to the origin of life on Earth. In particular, we propose a variety of potential applications in bioengineering and nanotechnology for the diverse self-assembled nanostructures.

Keywords: bioengineering; nanotechnology; origin of life; self-assembly; supramolecular structures; ultrasmall peptides.

Figure 1

Morphological characterization of the supramolecular structures formed by aliphatic ultrasmall peptides at low concentrations (close to or far below the minimum gelation concentration) using FESEM. Representative images of hollow nanospheres and blebs formed by (A) Ac-ID₃ (L) (5 mg/mL) at 8000×; (B) Ac-ID₃ (L) (2 mg/mL) at 2200×; (C, D) Ac-LD₆ (L) (0.1 mg/mL) at 4000× and 15,000× respectively; (E) Ac-AD₆ (L) (5 mg/mL) at 37,000×; (F) Ac-LD₆ (L) (1.3 mg/mL) at 6000×.

Figure 2

Representative pictures of hydrogels formed by self-assembling peptides containing aliphatic amino acids. Inverted vials show the formation of solid, stable hydrogels (A) Ac-ID₃ (L) 14 mg/mL; (B) Ac-AD₆ (L) 5 mg/mL; (C) Ac-LD₆ (L) 2.5 mg/mL.

Figure 3

Morphological characterization of the supramolecular networks formed by aliphatic ultrasmall peptides using FESEM. Representative images of fibers formed by (A, B) Ac-ID₃ (L) (15 mg/mL) at 30,000× and 100,000× respectively; (C, D) Ac-AD₆ (L) (5 mg/mL) at 30,000× and 95,000× respectively; (E) Ac-LD₆ (L) (10 mg/mL) at 35,000×; (F) Ac-LD₆ (L) (2 mg/mL) at 150,000×.

Figure 4

Representative pictures of hydrogels/aggregates formed by self-assembling peptides containing an aromatic amino acid at the C-terminus. Inverted vials show the formation of solid, stable hydrogels. (A) Ac-LF₆ (L) 10 mg/mL; (B) Ac-IF₃ (L) 5 mg/mL; (C) Ac-LY₆ (L) 10 mg/mL; (D) Ac-IY₃ (L) 5 mg/mL; (E) Ac-LW₆ (L) 10 mg/mL; (F) Ac-IW₃ (L) 5 mg/mL after 72 h.

Figure 5

Morphological characterization of the supramolecular networks formed by ultrasmall peptides containing an aromatic amino acid as head group using FESEM. Representative images of fibers formed by (A, B) Ac-LW₆ (L) (10 mg/mL) at 40,000× and 100,000× respectively; (C, D) Ac-IY₃ (L) (10 mg/mL) at 25,000× and 80,000× respectively; (E, F) Ac-IF₃ (L) (5 mg/mL) at 80,000× and 100,000× respectively.