Kinetic Switches: Exploiting Feedback in Enzyme Microparticles

Many biological processes require a rapid transition from one chemical state to another following a supercritical stimulus. These kinetically-controlled cell switches are driven by feedback such as autocatalysis, when a reaction is catalysed by its product. Feedback also lies at the heart of synchronisation of activity in cellular systems such as bacteria and yeast. There has been great interest in the design of reaction networks that produce feedback-driven behaviour, for example, genetic circuits were developed to create a toggle switch, chemical oscillations and synchronisation of oscillations in E. coli cells.

Through computational studies and experiments, we will design bio-inspired switches combining two components: feedback in the reaction kinetics and compartmentalisation of the reaction in microparticles. This research will provide insight into biological self-organisation as well as having potential applications in analytical or "smart" materials science.

The first component of the research involves designing novel reaction networks for chemical feedback and for this we will use nature's catalysts: enzymes. Enzymes offer specificity, efficiency and biocompatibility for widespread applications such as sensors, drug delivery devices and bio-reactors but the wealth of behaviour associated with autocatalysis has yet to be exploited. We will investigate possible advantages such as such as a fast, robust response to a chemical signal in the presence of noise.

In order to create a cellular switch, the enzyme catalyst for the reaction will be immobilised in microparticles. When immersed in a bath of reactants, the microparticles obtain chemical "fuel" from the surrounding solution, naturally maintaining the system far-from-equilibrium in a similar manner to cells. By manipulation of the kinetics, exciting features such as a chemical switch, hysteresis, chemical pulses, patterns or self-motion of the microparticles are possible. Groups of enzyme microparticles interact with each other via the release of chemicals into the surrounding solution, thus creating a new opportunity for the examination of collective behaviours and self-organisation in bio-inspired cellular systems.

The science of far-from-equilibrium self-organisation, or "complexity science", is of great interest to the general scientific community, as similar behaviours arising from feedback are observed in physics, chemistry, biology as well as the social sciences and are described by underlying mathematical principles. Recently, a new European initiative Euro-Chemistry held a meeting that "highlighted Complexity in Chemistry as one of the important areas where chemistry, in a collaborative effort with mathematics, must focus". This meeting also recognised that nonlinear chemical reactions, i.e. systems with feedback, are fundamental to this effort. We will produce a suite of enzyme reaction networks showing feedback-driven behaviour in silico, and bio-inspired enzyme microparticles that exhibit complex behaviour. Although our research is intended to uncover fundamental principles in far-from-equilibrium nonlinear systems, enzyme autocatalytic reactions and microparticles have potential applications in analytical and "smart" materials science. The research will therefore impact on a wide audience.

The development of autocatalytic enzyme microparticles will impact on scientists driven by a desire to mimic the complex structure and function observed in biology for useful applications. Although enzyme microparticles have been designed for a number of biotechnological applications, such as sensors, drug delivery devices and bio-reactors, the wealth of behaviour associated with autocatalytic reactions has yet to be exploited. Enzymes offer specificity, efficiency and biocompatibility for these applications; feedback gives potential advantages such as fast robust response over a wide range of conditions and in the presence of noise; periodic release of a chemical or synchronised activity overcoming diversity in a group of particles and self-motion of a particle. All of these features are well investigated in biological cell models but would be novel in applications utilising microparticles.

The researchers employed on the project will work as a cross-department, interdisciplinary team and will be trained in the tools of complexity/systems science. They will benefit from the combination of computational (kinetic) modelling and microparticle experiments with resulting skills that could be applied in many employment sectors. Additionally, project-related activities will be offered to PhD students, masters' and summer project students as well as to undergraduates through coursework.

The project is expected to produce visual results that can be communicated to the general public as well as resources that can be used to inspire young people into science. We will engage with local artists to bring particle behaviour to a wider audience through art instillations combining sound with oscillating particles. We will also offer a project-related workshop at science fairs and University initiatives. This will involve development of very a simple microfluidics device for coloured, responsive alginate microparticles, intended to highlight use of edible particles for healthcare, food science and sensing.