Reductionist Approach in Peptide-Based Nanotechnology

Abstract

The formation of ordered nanostructures by molecular self-assembly of proteins and peptides represents one of the principal directions in nanotechnology. Indeed, polyamides provide superior features as materials with diverse physical properties. A reductionist approach allowed the identification of extremely short peptide sequences, as short as dipeptides, which could form well-ordered amyloid-like β-sheet-rich assemblies comparable to supramolecular structures made of much larger proteins. Some of the peptide assemblies show remarkable mechanical, optical, and electrical characteristics. Another direction of reductionism utilized a natural noncoded amino acid, α-aminoisobutryic acid, to form short superhelical assemblies. The use of this exceptional helix inducer motif allowed the fabrication of single heptad repeats used in various biointerfaces, including their use as surfactants and DNA-binding agents. Two additional directions of the reductionist approach include the use of peptide nucleic acids (PNAs) and coassembly techniques. The diversified accomplishments of the reductionist approach, as well as the exciting future advances it bears, are discussed.

Keywords: bionanotechnology; molecular materials; molecular recognition; peptide engineering; self-assembly; supramolecular chemistry.

Figure 1

Hierarchal assembly of building blocks and the schematic representation of three molecular species that undergo a sequential self-organization process. Initially, the three types of molecules are randomly distributed. Then, one type of molecules undergoes self-assembly, and the two others are randomly distributed. In the next stage, a coassembled structure that contains two molecules is formed, and the third molecular species is in the solution. At the final stage, a three-component supramolecular structure is formed.

Figure 2

The fabrication of a power-generating device based on a diphenylalanine array. (a) Schematic of the diphenylalanine peptide-based generator connected to the measurement equipment. Bottom-right inset: photograph of a real device. The functional device was produced by Professor Rusen Yang from the University of Minnesota and coworkers. (b) Schematic of the measurement setup in which a linear motor pushes with controlled forces on the top electrode in panel a. (c) Photograph of the generator as a direct power source for a liquid crystal display (LCD). (d,e) Photograph of the LCD before (d) and after (e) the generator in (c) was pressed by a human finger. Modified from Reference under a Creative Commons CC-BY license.

Figure 3

Formation of superhelical supramolecular assemblies of a single heptad repeat with phenylalanines as interacting moieties stabilized by the incorporation of Aib, an α-methylated residue. The process of molecular self-assembly leads to the formation of ordered assemblies as observed using electron microscopy (scale bar is 100 nm). X-ray crystallography shows the organization into helical assemblies with the hydrophobic phenylalanines serving as interfaces between the helical elements. Modified from Reference following author reuse guidelines.

Figure 4

Coassembly as a strategy to tune dimensions and obtain new architectures. (a) Self-assembly of a single type of molecule forms elongated ordered assemblies. (b) The addition of a second species may control the assembly of the first type of molecule, resulting in structures of a more limited length. For example, the addition of Boc-diphenylalanine to diphenylalanine (as described in 161) led to the length of diphenylalanine nanotubes that were described in Section 5. (c) The addition of another type of molecular building block may lead to an alternative architecture. For example, the coassembly of diphenylalanine and triphenylalanine at a specific molar ratio leads to formation of noncanonical toroids (as described in 160).

Figure 5

Formation of peptide nucleic acid (PNA)-based assemblies. The PNA building blocks contain an amide bond. This type of bond is present in proteins, peptides, and the synthetic polyamide polymers (such as Nylon^® and Kevlar^®), described in Section 2.1. However, the side chains in PNA consist of nucleobases as in DNA or RNA. The process of molecular self-assembly leads to the formation of ordered assemblies, observed using electron microscopy (scale bar is 10 μm). X-ray crystallography shows them in a stacked assembly similar to the dipeptide assemblies described in Section 5. However, in addition, there are Watson-Crick hydrogen bonds like those observed in nucleic acid structures. Modified from 34 following author reuse guidelines.