Artificial organelles encapsulating autocatalytic enzyme reactions for application in controlled release and chemotactic transport

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Enzyme autocatalysis can lead to a feedback response that allows the development of chemical switches, toggles and oscillators. The non-linear response of these systems have potential applications in responsive soft materials for developing healthcare technologies.We will aim to develop responsive vesicles that respond to metabolites in their environment by (i) chemotaxis (active motion towards or away from high concentrations of substrate), and (ii) triggered release of therapeutic compounds. This project will confine autocatalytic enzyme reactions inside the lumen of vesicle-based "artificial organelles". These artificial organelles will have a non-linear response to the presence of the confined enzyme, producing a biochemical switch that activates a desirable change in system properties. Firstly, we will characterise and understand the motility of these vesicles in the presence of their substrate and in substrate concentration gradients. This understanding will enable the development of particles that can swim to target locations within complex media. Secondly, we will develop systems that exhibit controlled release in response to a metabolite and demonstrate this application in experimental drug delivery model systems. This will enable the triggered release of therapeutic compounds at a target location or with a desired change in the local environment.The project will begin with encapsulating the well-studied autocatalytic urea-urease reactions inside vesicles but will then broaden to study other autocatalytic metabolite-enzyme combinations. Ultimately this research will aim to develop a generalised approach to creating metabolite-triggered vesicles with applications in artificial cells and nanomedicines.