Tailor-Made Functional Peptide Self-Assembling Nanostructures

Abstract

Noncovalent interactions are the main driving force in the folding of proteins into a 3D functional structure. Motivated by the wish to reveal the mechanisms of the associated self-assembly processes, scientists are focusing on studying self-assembly processes of short protein segments (peptides). While this research has led to major advances in the understanding of biological and pathological process, only in recent years has the applicative potential of the resulting self-assembled peptide assemblies started to be explored. Here, major advances in the development of biomimetic supramolecular peptide assemblies as coatings, gels, and as electroactive materials, are highlighted. The guiding lines for the design of helical peptides, β strand peptides, as well as surface binding monolayer-forming peptides that can be utilized for a specific function are highlighted. Examples of their applications in diverse immerging applications in, e.g., ecology, biomedicine, and electronics, are described. Taking into account that, in addition to extraordinary design flexibility, these materials are naturally biocompatible and ecologically friendly, and their production is cost effective, the emergence of devices incorporating these biomimetic materials in the market is envisioned in the near future.

Keywords: bioelectronics; hydrogels; nanostructures; peptides; self-assembly.

Figure 1. Schematic presentation of peptide assembly into helix and β-sheets. Dashed lines represent hydrogen bonding networks facilitating the assembly process.

Figure 2

β-Sheet forming designs. Light blue and red represent designated hydrophilic and hydrophobic segments of the peptide, respectively. Side chains were omitted for clarity. Schematic representation of common self-assembled β-sheet structures is depicted, with dashed light blue and pink lines showing the direction of hydrogen bonds and π-stacking, respectively. Note that the cyclic peptide design is an example from a family of cyclic designs consisting of _D,L-α-peptides (the gray color represents unspecified requirement for the nature of side chains).

Figure 3

Sensing enzyme catalysis of phoshosphorylation and dephosphorylation processes using SAM of peptides on gold. A dense monolayer of peptides on a gold electrode undergoes phosphorylation that causes disruption of the monolayer order and leads to a change in the surface impedance. Removal of the phosphate groups induces reordering of the monolayer. Figure 3 is based on data in refs.^[–45].

Figure 4

De novo designed peptide based antifouling coating. a) Conceptual design approach: the peptide design includes three functions: adsorption to the surface by a sticky amino acid, self-assembly motif of aromatic amino acids, and antifouling motif by incorporation of fluorine atoms. b) Chemical structure of the peptide NH₂–DOPA–(4F)Phe–(4F)Phe–COMe. c) Schematic presentation of spontaneous coating of the surface with a peptide monolayer by a dip-coating process. Figure 4 is based on data in ref. [70].

Figure 5

Surface modification by self-assembled peptides particles. a) Peptide nanowires array formed after treating FF with pentafluoroaniline. A water contact angle shown in the inset indicates the formation of a superhydrophobic surface. Reproduced with permission.^[80] Copyright 2009, RSC. b) Surface patterning using nanofibers of PAs, including holes, channels, and posts. Reproduced with permission.^[82] Copyright 2009, RSC. c) Hexagonal monolayer arrangement of self-assembled Boc–Phe–Phe–Phe bio-nanospheres as fabrication patterning masks. Reproduced with permission.^[83] Copyright 2010, Wiley-VCH.

Figure 6

ET in peptide molecular bridges. Schematic depiction ofET mechanisms through a helical peptide bridging a gold substrate, and an atomic force microscopy tip (a common experimental setup to study ET through monolayers). The dependence of the current (I) on the length of the molecule (L) is depicted below, demonstrating a crossover between tunneling and hopping dominated ET, depending on the length of the molecule. A crossover point at 1 < L < 2 nm, indicated by a change in the current decay coefficient, β, has been reported. Figure 6 is based on data in refs. [94,95,97,99].

Figure 7

Effect of side chain on charge transport. Effects induced by the choice of charged/aromatic side chains are shown at the left/right I–V curves, respectively. Data were collected at 70% relative humidity/vacuum for the left/right panels, respectively. The structure of the “native” Aβ peptide used in these studies is shown below. Schematic depiction of current measurement setup is shown to the left, together with an atomic force microscopy image of the fibers. Reproduced with permission.^[122] Copyright 2014, Wiley-VCH.

Figure 8

Hydrogel structure and organization. Discrete building blocks self-associate to form a noncovalent supramolecular structures. The binding forces may include aromatic, electrostatic, and hydrophobic interactions. The interaction of the formed supramolecular networks with water molecules in a gelation process results in the attainment of macroscopic semirigid structure that can contain more than 99% water.