Applications of peptide and protein-based materials in bionanotechnology

Abstract

In this critical review we highlight recent advances in the use of peptide- and protein-related materials as smart building blocks in nanotechnology. Peptides and proteins can be very practical for new material synthesis and device fabrications. For example, peptides and proteins have superior specificity for target binding as seen in the antibody recognition and this biological recognition function can be used to assemble them into specific structures and shapes in large scale, as observed in the S-layer protein assembly. Collagens are assembled from triple helix peptides in micron-size with precise recognition between peptides and these biological assemblies can undergo smart structural change with pH, ionic strength, temperature, electric/magnetic fields. In addition, assemblies of peptides can template complex 3D crystallization processes with catalytic function, thus enabling to grow various materials in physiological conditions at low temperature in aqueous solution. The biomimetic growth of nanomaterials in aqueous solution is extremely useful when they are applied to therapeutics and medical imaging in vivo since these nanomaterials will be well dispersed in bodies. Peptides also play significant roles in signal transduction pathways in cells. For example, neuropeptides are used as neurotransmitters between synapses and these peptides bind receptors on the surface of cells to cascade the signal transduction. These versatile functions of peptides are extremely practical and here we discuss them with examples of relevant applications such as nanoreactors, sensors, electronics, and stimulus-responsive materials. It should be noted that peptide/protein assemblies can be applied to build up micron-scale materials that still feature excellent nano-scale ensembles, which essentially bridges the nano-world and the micro-world (86 references).

Fig. 1

(a) A proposed structure of the Cu nanocrystal–HG12 peptide complex on the template nanotube. The conformation change of peptides influences the nucleation and the growth rate to control the Cu nanoparticle domains on bionanotubes. (b) Cu nanocrystals grown on the bionanotube at pH 6; (top-left) TEM image. (top-center) Electron-diffraction pattern. (top-right) Size distribution. (inset) The TEM image in higher magnification. (bottom). (c) Cu nanocrystals grown on the bionanotube at pH 8; (bottom-left) TEM image. (bottom-center) Electron-diffraction pattern. (bottom-right) Size distribution. (Inset) The TEM image in higher magnification. (Scale bar = 100 nm.)

Fig. 2

Peptide and protein nanoreactors; (a) Illustration of mono-disperse silver nanoparticle growth inside the cavity of a peptide polynanoreactor; (b) TEM image of peptide nanorings assembled from bolaamphiphile precursor grow β-Ga₂O₃ inside their cavity; (c) TEM image of silver nanoparticles synthesized inside the genetically engineered protein cage apoferritin; (d) TEM image and SAED pattern of highly crystalline ZnO nanoshells grown at room temperature by using the enzyme urease as a biocatalytic template for the reaction. (a,d reproduced with permission from ref. and , copyright Wiley-VCH Verlag GmbH & Co. KGaA; b, c, reprinted with permission from ref. and , copyright 2007, 2004 American Chemical Society).

Fig. 3

Protein nanopore sensors detect a current decay as single stranded DNA molecules are translocated trough the pore. (reprinted by permission from Macmillan Publishers Ltd: Nature Biotech., ref. 55, copyright 2008).

Fig. 4

Impedimetric pathogen biosensors assembled from peptide nanotubes; (a) antibody modified nanotubes concentrate virus at the gap between two electrodes and the impedance at high frequency increases; (b) peptide nanotube biochips for the multiplexed detection of bacterial cells via agglutination on an array of impedimetric transducers.

Fig. 5

Transport mechanism of the protein FET. The monolayer of the blue-copper protein azurin, containing the central Cu ion as redox site, connecting two arrow-shaped Cr/Au electrodes on a SiO₂ substrate. An Ag back-electrode acts as the gate. The transport is based on sequential electron hopping between one reduced azurin (blue copper ion in the inset) to an adjacent oxidized one (red ion in the inset). The vertical gate can influence the oxidation state of the redox site to induce the field effect. (reproduced with permission from ref. 65, copyright Wiley-VCH Verlag GmbH & Co. KGaA).

Fig. 6

Assembly of ferritin-Co₃O₄ composites between source and drain electrodes (left) and the cross sectional TEM of the device showing Co₃O₄ nanoparticles embedded in the control SiO₂ layer after proteins are sintered (right). (Reproduced by permission of The Royal Society of Chemistry).

Fig. 7

Scheme to assemble two different antibody nanotubes, anti-mouse IgG-coated nanotube and anti-human IgG-coated nanotube, into the cross-bar geometry by biomolecular recognition (left). AFM image of the two antibody nanotubes assembled in the cross-bar geometry (right). Scale bar = 200 nm.

Fig. 8

(a) Schematic of the peptide vapor deposition technique. Low-molecular weight diphenylalanine peptides are vaporized from a bottom substrate heated at 220 °C in the form of a cyclic structure and deposited on the upper substrate at 80 °C to form ordered vertically aligned peptide nanotubes. (b) Side view SEM image of vertically aligned peptide nanotubes on a carbon substrate. (reprinted by permission from Macmillan Publishers Ltd: Nature Nanotech., ref. 78, copyright 2009).

Fig. 9

Schematic representation of ELP fusion protein actuators. When apoCaM (a) binds Ca²⁺, the attached ELPs are assembled into meso–microscale particles (b). Chelation of the bound Ca²⁺ by EDTA reverses the LCST transition to the apoCaM–ELP monomers. Legend: CaM, cyan; ELPs, orange; Ca²⁺, gray. (reprinted with permission from ref. 79, copyright 2008 American Chemical Society).

Fig. 10

(A) The actuator peptide, consisting of negative and positive residues, is designed to release positively charged parts by enzymatic reactions. (B) The scheme of the actuation motion. The positive charges generated by enzymatic cleavage of the bond between alanine residues swells protein particles via charge–charge repulsion. The enzymatic cleavage also leads to diffuse cationic proteins through the polymer pores as payload release. (reproduced by permission of The Royal Society of Chemistry).

Fig. 11

(a) Squid, Loligo pealeii, adjusts the spacing and thickness of multilayers of proteins to control refractive indexes. (b) TEM image of the squid iridophores, protein refractive platelets. Scale bar = 1 μm. (c) Reflectin-mimetic biopolymer platelets that change the spacing by electrochemical reactions (d₃ < d₂ < d₁). (a, b, reproduced with kind permission from Springer Science; c, reproduced with permission from ref. 86, copyright Wiley-VCH Verlag GmbH & Co. KGaA).