Bacteriophages (phages) are bacterial viruses. Phages offer remarkable diversity and can be found in many shapes and sizes; however, what they all have in common is that they are made of protein nano-shells that encase their genome (DNA or RNA). In other words, phages are proteinous bionanoparticles. In this work, we use the filamentous phage M13. M13 is a simple virus with a high aspect ratio. It has 11 genes and only 5 structural proteins. The phage filament is almost entirely made of 2700 copies of pVIII, the major coat protein, and is capped off on one end by five copies each of the proteins pIII and pVI, while the opposite end displays five copies each of the proteins pVII and pIX. M13 phage can be genetically engineered to display certain peptides with affinity toward cancer cells, specific tissue, or even minerals and polymers. These filaments can further self-organize to form liquid crystals at high concentrations. All these properties make M13 a unique building block for the bottom up synthesis of advanced bioactive material.
The objective of my proposed research is to develop hydrogels using M13 phage. Hydrogels can absorb large quantities of water without dissolving. They mark a breakthrough in the field of biomaterials, owing to their high water content, porosity and soft consistency. I crosslinked M13 at liquid crystalline concentrations using glutaraldehyde. The resulting hydrogels were characterized for swelling and mechanical properties. These hydrogels exhibited self-healing and autofluorescence properties. In addition, I demonstrated that M13 can from self-healing hydrogels at lower concentrations by adding the small globular protein, BSA.
The developed M13 hydrogels mark the first step in the development of bioactive hydrogels that could be utilized to direct cell destiny and genuinely mimic the natural tissue. / Thesis / Master of Applied Science (MASc) / Filamentous phage are viruses that infect bacteria. These bio-filaments are ~1 𝜇𝑚 long, 6-8 nm in diameter and can propagate themselves by infecting bacteria. This means one bio-filament can make 300-1000 particles only by infecting a bacterial host, a characteristic that drastically increases their utility over synthetic filamentous nanomaterial. Filamentous phage can be readily genetically engineered to express foreign receptors on their surface. In this thesis, I demonstrate how these bio-filaments can self-organize at high concentrations and can be crosslinked to make hydrogels that can adsorb up to 12 times their weight in water. These hydrogels can also heal themselves if broken or cut and exhibit autofluorescence, which are very useful properties for hydrogels used for biomedical applications. We further demonstrate that adding small proteins to the bio-filaments can expand the range of hydrogel formation, to the extent that even low concentrations of bio-filament can form hydrogels.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/24014 |
| Date | January 2018 |
| Creators | Peivandi, Azadeh |
| Contributors | Hosseini-Doust, Zeinab, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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