Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials

Abstract

Twelve derivatives of peptide-amphiphile molecules, designed to self-assemble into nanofibers, are described. The scope of amino acid selection and alkyl tail modification in the peptide-amphiphile molecules are investigated, yielding nanofibers varying in morphology, surface chemistry, and potential bioactivity. The results demonstrate the chemically versatile nature of this supramolecular system and its high potential for manufacturing nanomaterials. In addition, three different modes of self-assembly resulting in nanofibers are described, including pH control, divalent ion induction, and concentration.

Figure 1

Chemical structure of PA 4.

Figure 2

Time sequence of pH-controlled PA self-assembly and disassembly. (Upper) From left to right molecule 6 dissolved in water at a concentration of 0.5% by weight at pH 8 is exposed to HCl vapor. As the acid diffused into the solution a gel phase is formed, which self-supports upon inversion (Far Left). (Lower) The same gel is treated with NH₄OH vapor, which increases the pH and disassembles the gel, returning it to a fully dissolved solution.

Figure 3

Light microscopy image of a gel formed from PA 4 between crossed polarizers. Birefringence indicates orientation of the material at the level of tens of microns.

Figure 4

TEM image of fibers formed from molecules 3 (a) and 5 (b). Samples were negatively stained with phosphotungstic acid.

Figure 5

Schematic illustrating the self-assembly and covalent capture of the PAs based on pH and oxidation state. Molecules self-assemble upon acidification and dissassemble at neutral and basic pH when fully reduced. Molecules that are oxidized will not self-assemble at acidic pH, likely because of the distorted conformation required by intramolecular disulfide bonds. Supramolecular fibers that are oxidized (polymerized) lose their sensitivity to pH and are thus stable across a much broader range of pH, including physiological.

Figure 6

TEM image of fibers formed from molecules 6 (a) and 7 (b). Samples were negatively stained with phosphotungstic acid. PA 6 displays a strong tendency to form parallel arrays of fibers whereas PA 7 does not.

Figure 7

TEM images of fibers formed from molecules 9 (a), 11 (b), and 12 (c). Samples were negatively stained with phosphotungstic acid. Although fibers with a diameter between 5 and 8 nm are formed in all cases, the length and stiffness of the fibers formed vary considerably.

Figure 8

TEM images of molecule 3 (a) self-assembled by drying directly onto a TEM grid without adjusted pH and molecule 4 (b) self-assembled by mixing with CaCl₂. Molecule 3 is negatively stained with phosphotungstic acid whereas molecule 4 is positively stained with uranyl acetate. In both cases the same fibrous morophology is observed as is seen by pH-induced self-assembly.