Bacteriophages in Nanotechnology: History and Future

Abstract

Bacteriophage (phage) proteins and whole phage particles are being used in the development of new functional materials with nanoscale features. Bacteriophage capsids and accessory structures (tails, tail fibers, etc.), based on size scale, can be considered evolved protein-based nanotechnological structures. Because of the ease of genetic manipulation, bacteriophages are a useful system for developing proteins with applicability to functional material development. Most of these materials fall into two categories – biological sensors and biologically/chemically active peptides. Biological sensors may take advantage of a bacteriophage’s natural tropism for its host bacteria, although this tropism can be modified. Peptides that can be used to create new materials are typically isolated using phage display, a process for identifying peptides with specific binding capacities from a random peptide library. In this review, we describe some of the methods used to create these materials and their potential applications. This has mostly been done in laboratory studies as very few of these materials have been developed into commercialized products. We conclude with a discussion of the challenges to commercialization of the phage-based materials.

Glossary

Adhesin

Most generically, any protein or other structures a microbe uses for attachment, but in this chapter a bacteriophage adhesin is essentially the same as the receptor binding protein.

Antigen binding region

In an antibody or related molecule, the region that actually contacts and has affinity for the antigen; elsewhere this is also called the epitope binding region.

Binding affinity

The strength of interaction between two molecules, one of which binds the other.

Binding peptides

In general, a peptide with binding affinity for some target molecule; more specifically a peptide in a phage or other display library with affinity for a target molecule or material.

Bionanotechnology or nanobiotechnology

The field of science or technology concerned with using biological molecules such as proteins or nucleic acids to create a material with nanoscale functional features.

Biosensor

A sensor that detects the presence of some microorganism or other biological molecule.

Biotin/biotinylation

Biotin is a small organic molecule that can be attached to proteins (biotinylation) to act as an attachment site for streptavidin or avidin, which is usually attached to some detection molecule. Thus, the biotin-streptavidin acts as an attachment linkage between two molecules that otherwise have no affinity for each other. Biotin is attached to biotinylation sites within a protein (naturally or by genetic engineering) by enzymes normally found in E. coli or other protein expression systems.

Carbon nanotube

Cylindrical nanostructures composed of carbon with an extended fullerene structure. Carbon nanotubes can be chemically modified using a variety of organic chemistry reactions to attach other molecules as linkers for attachment. Carbon nanotubes have useful optical, thermal, electrical, and other properties for materials applications.

Cell wall binding domain (CBD)

The domain in endolysins with affinity for a bacterial cell wall component.

Conjugation

In the context of this chapter, conjugation refers to the joining of two entities via a chemical linkage.

Liquid crystal

A phase of matter in which molecules form ordered crystalline regions under certain conditions but can become disordered when conditions change. Properties such as ability to flow, optical properties, and others may be quite different between the two conditions making liquid crystals useful as sensors or transducers.

Nanocrystal/nanoparticle

A particle of uniform composition with at least one dimension measuring less than 100 nm. Quantum dots are a subset of nanocrystals. Nanocrystals may be coated with other materials increasing their size above the nanoscale without loss of some useful nanocrystal properties.

Nanomaterials

A general term for any material with a functionality due to some nanoscale feature or molecule.

Nanoscale (nanoscopic scale)

A size scale between 1 and 100 nm.

Paramagnetic bead

Beads usually made of iron oxide that are magnetic and attracted to an external magnetic field but not magnetic in the absence of the external field. Paramagnetic beads are typically too large to be nanoparticles.

Piezoelectric

The property of a material that gains an electrical charge in response to mechanical stress. Piezoelectric materials may be inorganic or organic.

Quantum dot

A nanocrystal of a semiconductor material whose size and composition result in it acting as a single atom with electron energy state transitions being quantized. Physical properties such as absorption and emission of light will be different in quantum dots of the same composition, but different sizes although chemical properties will be identical.

Self-assembly

A process in which subunits assemble into an ordered structure based in internal properties without external, nonstructural components. Bacteriophage capsids and appendages are often described as self-assembling although they may require a few nonstructural proteins (chaperones) for complete assembly.

Semiconductor

A material typically composed of one or more of the metalloid elements whose conductivity is less than a metal conductor but more than a nonmetal insulator. Semiconductors’ electrical properties can change in response to external stimuli such as electrical fields or temperature. They are used in construction of transistors and integrated circuits.

Single-chain antibody (ScFv)

An antibody-like protein in which the heavy and light subunits are joined into a single polypeptide. These proteins may be derived from naturally made camelid single-chain antibodies or by genetic engineering of mammalian four-chain antibodies to fuse the light and heavy chain binding domains into a single polypeptide. ScFvs have just a single antigen binding domain per molecule; hence they are also described as single-domain antibodies.

Tag

Any peptide sequence added to a protein to allow for binding of a marker entity for detection or other purposes. In some embodiments, the tag is a large marker such as GFP.

Transduction or signal transduction (non-biological, not phage transduction of genetic material)

In the context of this chapter, transduction methods are ways of converting the binding of a molecule to a biosensor into a detectable signal. The output signal may be mechanical, optical, or electrical. Details of methods discussed in this chapter are found in the section “Signal Transduction Methods.”