Filamentous Phages as Building Blocks for Bioactive Hydrogels

Abstract

Filamentous bacteriophages (bacterial viruses) are semiflexible proteinous nanofilaments with high aspect ratios for which the surface chemistry can be controlled with atomic precision via genetic engineering. That, in addition to their ability to self-propagate and replicate a nearly monodisperse batch of biologically and chemically identical nanofilaments, makes these bionanofilaments superior to most synthetic nanoparticles and thus a powerful tool in the bioengineers’ toolbox. Furthermore, filamentous phages form liquid crystalline structures at high concentrations; these ordered assemblies create hierarchically ordered macro-, micro-, and nanostructures that, once cross-linked, can form hierarchically ordered hydrogels, hydrated soft material with a variety of physical and chemical properties suitable for biomedical applications (e.g., wound dressings and tissue engineering scaffolds) as well as biosensing, diagnostic assays. We provide a critical review of these hydrogels of filamentous phage, and their physical, mechanical, chemical, and biological properties and current applications, as well as an overview of limitations and challenges and outlook for future applications. In addition, we present a list of design parameters for filamentous phage hydrogels to serve as a guide for the (bio)­engineer and (bio)­chemist interested in utilizing these powerful bionanofilaments for designing smart, bioactive materials and devices.

Bacteriophage‐built gels as platforms for biomedical applications

“…Diverse size and shape: Phages have an enormous diversity of physical structures, both in shape and size. [30] They are either icosahedral, filamentous, or head-tail in shape, and their size can vary from a few nanometres to over one micrometre (Figure 1). It provides abundant options to design phage-built materials according to the aiming structures and applications.…”

“…They are excellent nanoparticles for constructing nanomaterials based on the following properties: Diverse size and shape: Phages have an enormous diversity of physical structures, both in shape and size. [ 30 ] They are either icosahedral, filamentous, or head‐tail in shape, and their size can vary from a few nanometres to over one micrometre (Figure 1). It provides abundant options to design phage‐built materials according to the aiming structures and applications. Sophisticated inner structure: The protein arrangement on the phage capsids is remarkably intricate.…”

Gelatin-methacryloyl hydrogels containing turnip mosaic virus for fabrication of nanostructured materials for tissue engineering

“…For example, nanoparticles have been functionalized with growth factors (Fathi-Achachelouei et al, 2020), peptides (Babitha et al, 2018), cell attachment sites (Lee et al, 2016), antioxidant molecules (Di et al, 2020), and antibacterial compounds (Godoy-Gallardo et al, 2021), among others. Naturally occurring nanoparticles, such as filamentous viruses (i.e., bacteriophages and plant viruses), are now also increasingly recognized as promising nanomaterials and are showing wide use in tissue engineering (Merzlyak et al, 2009;Lauria et al, 2017;Lin et al, 2020;Dickmeis et al, 2021;Jackson et al, 2021;Venkataraman and Hefferon, 2021) and other biomedical applications (Steinmetz and Evans, 2007;Peivandi et al, 2021).…”

“…The dimensions of filamentous viruses vary between 300 and 900 nm in length and 7 and 15 nm in width (Koudelka et al, 2015). Molecular cloning has enabled the production of viruses as long as 8,000 nm (Jackson et al, 2021). A frequent feature of filamentous viruses is that their capsid consists of a single coat protein (CP) that is repeated thousands of times (Zanotti and Grinzato, 2021).…”

A possibility of polaron vortex magnet of polypyrrole prepared in virus liquid crystal

“…The fd phage/conjugated polymer composite was investigated, and a cube of phage‐polymer was realized 3 . Virus‐based piezoelectric energy generation, 4 virus/polyethylenedioxythiophene (PEDOT) nanowires for bio sensors, 5 conducting polymers bearing human influenza‐sensing function, 6 conducting polymer‐based COVID‐19 detector, 7 high thermal diffusivity in filamentous M13 phage, 8 virus‐based fabrictions, 9 fabrication of virus fibers, bioactive hydrogels, 10 and chemically modified viruses, 11 have been reported. An M13KE bacteriophage‐based structural colorimetric sensor was developed 12 .…”