Polymers, proteins and cells
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Biopolymers such as proteins, nucleic acids and polysaccharides are essential components in living systems and enabling the modification and modulation of various cellular functions and cellular behaviour. Many synthetic polymers have been used in a cellular context mimicking these natural polymers. However, few studies have focused on polymerisation chemistry within the complicated biological environment inside cells. In the first part of this thesis, a new method of synthesising synthetic polymers in cells was developed, enabling the introduction of artificial components to tune cellular behaviour. Several biocompatible acrylic and styrene monomers were polymerised intracellularly and shown to control the cell cycle, alter the cytoskeleton and influence cell motility. Moreover, the introduction of specific functional monomers enabled the in situ formation of fluorescent polymers and nanoparticles which may contribute to further applications such as fluorescent imaging and cargo delivery. Chemical modifications of native biomacromolecules provides access to novel functions such as macromolecule based cargo delivery and imaging probes. In the second part of this thesis, linear acrylamide polymer scaffolds, bearing norbornene reactive centres for tetrazine ligation and a hexahistidine tag for ease of purification, were synthesised and conjugated to a clinical antibody. This enabled the selective labelling of cancer cells with amplified fluorescent signal. Simultaneously “switching on” and amplification of a fluorescent signal “in situ” were achieved by utilising a tetrazine quenched fluorophore, reacting with norbornenes on the polymer–antibody conjugate. This fluorescence signal amplification method has the potential to improve real-time tumour detection and fluorescence-guided surgeries while the amplification strategy can be expanded to enhance radio-therapy performances.