Protein-based nanotechnology combines the study of nanoscale proteins with the expanding field of nanotechnology. Proteins are versatile biomolecules, composed of amino acid chains, which provide the foundation for important biological functions such as molecule transportation and DNA replication.

The protein structure also makes them suitable for forming functional biological materials as well as their ability to self-assemble. The resulting developments in protein-based nanotechnology include proteins being utilized as important elements in nanotechnology applications, along with applying nanodevices to the biological environment where proteins are contained.

Proteins in Nanomachine Assembly

Proteins are suitable for use in material development and for building nanoscale machines because they provide similar roles in biology. The complex protein formations that occur in the biological environment include rings, tubes and cages, potential building blocks for nanomachines. Nanoscale component assembly is problematic because the small dimensions involved cause difficulty in manipulation. The utilization of proteins provides a solution as they show natural affinity to other biomolecules and can spontaneously self-assemble. By engineering protein affinities, nanodevices can self-assemble when individual components are mixed. However, protein engineering has been hindered by the difficulty of designing specific self assembling proteins because of chemical heterogeneity and the large scale surfaces required for protein-protein interaction.

A strategy for forming a controlled assembly of protein nanostructures was developed in 2015. Gold nanoparticles are employed as scaffolds allowing for directed interfacial interaction. A protein is chosen with a known affinity to the target proteins being assembled. The chosen protein is then grafted onto the gold nanoparticles and assembly is performed through protein pair formation. The technique has the potential to be optimized for functional nanomaterial engineering as well as applications in biosensing and cell targeting.

Proteins as Nanowires for Biosensing

Nanowires are slender structures with a diameter at the nanoscale. Their application is not limited to the physical sciences with increasing use in the biosciences, particularly in biosensing studies. Biological structures such as DNA have previously been assessed as material for nanowires but there are questions about the inherent conductivity of DNA.

The advantages to the application of proteins for constructing nanowires include:

The natural occurrence of fibrous protein structures is particularly suited to the formation of self-assembled nanowires. Fibrous proteins also have greater stability than globular proteins. The basic amino acid chain structure of proteins allows for the exploitation of amino acid chain chemistry, including as a base for metallic modification. Genetic control of the primary sequence forming the amino acids provides further opportunity for increased functionalization. Proteins can be generated in large amounts and can provide a readily available source material.

Biosensing involves the detection of biological and chemical molecules at the nanoscale through signal transduction. It is therefore advantageous to develop signal transduction pathways at the same scale. Proteins and peptides have been used to create a biosensing device through the modification of electrodes to create a porous nanowire. A protein enzyme is immobilized onto the protein nanotube or nanofiber via cross-linking molecules. This structure is then attached to an electrode. The biosensing device formed is capable of applications such as glucose sensing, by the covalent bonding of glucose oxidase to the protein nanotube complex. The employment of this technology is particularly important in diabetes management.

Nanotechnology and Proteomics

Nanotechnology is also being applied to the study of proteomes, the complete set of proteins expressed by a cell or organism. An important aspect of proteomics is the ability to profile proteins and their interactions. Nanotechnology has allowed for the miniaturization of platforms providing a high-throughput method of analyzing thousands of proteins simultaneously. This had led to advances in biomarker identification, immunological profiling and vaccine development. Analysis at the nanoscale also provides the ability to reduce sample and reagent volumes whilst increasing sensitivity.

By Shelley Farrar Stoakes, MSc, BSc

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