Development of Gold Nanoparticle based Photo-responsive Inorganic Prototissues

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First proposed by Dr. Thomas Ming Swi Chang in 1957, the concept of artificial cells, or protocells, serves to provide researchers with deeper insights into primitive cellular functions and behaviours through the study of abiotic cellular analogues. Protocells are synthetic, cell-like microcompartments designed to mimic key aspects of living cells, such as spontaneous growth and division, phagocytosis, and gene-directed protein synthesis, to name a few. In the past decade, a range of different synthetic protocell models have been developed based on lipid vesicles, self-assembled polymers, inorganic colloidal microcapsules (colloidosomes), semi-permeable protein-polymer nano-conjugates, and more. Many research teams are currently focusing on increasing the levels of bio-functionality and autonomy of these materials by advancing the protocells biochemical complexity using top-down methodologies. The research group of Dr. Pierangelo Gobbo have made remarkable steps forward in the field through utilizing bioorthogonal click chemistry to covalently assemble protocells into tissue-like constructs, termed prototissues. These chemically interlinked prototissues display collective thermally regulated contractibility that can be enzymatically modulated and exploited for mechanochemical transduction. Most importantly, this work allowed for the first synthetic route to fabricate tissues-like materials capable of collective behaviours.Among the different protocell models, inorganic colloidosomes are receiving growing attention due to their relevant benefits compared to their biological counterparts, such as increased chemical, thermal and mechanical robustness. While inorganic protocell membranes have been prepared from silica or magnetic nanoparticles, the use of functional gold nanoparticles (AuNPs) remains essentially unexplored. AuNP interfaces can be engineered to undergo a plethora of interfacial, bio-orthogonal, click reactions for the chemo-selective capture and release of complementary molecular systems in complex environments. This research aims to fabricate polymer-coated AuNPs as simple building blocks capable of self-assembly into functional gold colloidosomes. The photo-responsive nature of AuNPs allows for light conversion into localized heat through surface plasmon resonances, triggering the lower critical solution temperature of the thermo-responsive polymers coating the AuNPs. These protocells can then be covalently cross-linked into prototissues, capable of collective photo-regulated contractibility that can be enzymatically modulated. The goal of this project at its core is to explore the interface between living matter and non-living matter and pioneering ground-breaking scientific advancements towards the generation of protocellular materials from AuNP-based colloidosome building blocks. This research project is highly multidisciplinary, adventurous and aims to open new frontiers in bottom-up synthetic biology by merging for the first time the field of functional nanomaterials with aspects of protocellular bio-design and construction. The proposed research is expected to lead to the first inorganic, protocellular materials that could be employed for applications in photothermal therapy, biosensing, and drug delivery. This project is joint between the University of Bristol and the University of Western Ontario through a cotutelle program and falls within the EPSRC physical sciences (synthetic biology) research area.