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Magnetic micromachines based on protocell design and engineering

Periodic Reporting for period 1 - MagProtoCell (Magnetic micromachines based on protocell design and engineering)

Reporting period: 2015-05-01 to 2017-04-30

The main objective of MagProtoCell was the design and construction of magnetic field-sensitive protocells (i.e. artificial cell-like entities) whose motility could be remotely controlled by an external magnetic field. In doing so, a new class of magnetic micromachines will be developed capable of delivering biomimetic functions embedded within the protocellular compartments such as enzyme-mediated catalysis, gene expression, etc. to localized sites under precise temporal and spatial control. From an applied point of view, enabling controlled motility of protocells in fluidic environments is crucial for the development of emerging applications of potential impact on energy production, public health and environmental issues such as clean-up of trace pollutants, clinical diagnosis, targeted drug delivery, control of microscale bioreactions or lab-on-a-chip devices. Some of these applications can be considered as Key Enabling Technologies (KETs), which will foster the Industrial Leadership pillar of Horizon 2020 (H2020) and the development of a European bioeconomy.
The work performed during these two years has resulted in the construction of magnetic-field responsive protocells. In particular, we have designed water-in-oil magnetic Pickering emulsion (MPE) droplets delineated by a membrane of iron oxide (magnetite) nanoparticles of adequate size (around 500 nm) to enable magnetic field-guided motion. The application of the magnetic field resulted in the formation of chain-like arrays of MPE droplets aligned parallel to the magnetic field direction. Furthermore, the magnetic membrane was engineered to produce localized particle-free apertures upon the addition of a fatty acid to the external oil medium. We have shown that these apertures could be exploited to engulf a second population of protocellular droplets (i.e. silica nanoparticle-stabilized) leading to phagocytosis-inspired behaviour. By using external magnetic fields the phagocytosis behaviour can be improved in two ways: (i) by displacing the magnetic particles of the shell to facilitate engulfment, and (ii) by attracting the MPE droplets to areas enriched in the target droplets to increase the overall efficiency of the process (i.e. enabling higher number of phagocytosed objects). We have also demonstrated that the engulfed colloidosomes can deliver and release water-soluble payloads to trigger an enzyme reaction inside the host MPE droplets. These results constitute a first step towards the construction of protocells with higher-order functions able to interact in mixed populations (i.e. communities). The main results of the project have been disseminated using different channels depending on the target audience. In a scientific context, two manuscripts of scientific articles have been prepared. The first one has been published in the journal Nature Materials (doi; 10.1038/nmat4916). The article has been highlighted in the journal Nature Review Materials (doi:10.1038/natrevmats.201741). Also, an image of the article will be used as banner of the website of Nature Materials. The second article is still in preparation. When the articles are published, we will make use of press releases (the University of Bristol press office has collaborated in this for the first article), newsletters and advertisement in social media such as ResearchGate to increase their visibility. In addition, and following the regulations of Horizon 2020, the publications are/will be deposited in the repository of the University of Bristol, PURE, and will be made open access (the first article is still under embargo, its PURE ID number is 110696786). In addition to scientific articles, the results have been presented in the following scientific conferences: Gordon Research Conference in Biointerfaces (2016), BrisSynBio Conference (2016), 5th International Conference on Multifunctional, Hybrid and Nanomaterials (2017) and invited talks at Imperial College London (Prof. Stephen Mann, 2016) and in a Summer School at the University of Paris-Diderot (Dr. Laura Rodriguez-Arco, 2017). In a more general approach, we have worked in collaboration with the Centre for Public Engagement of the University of Bristol to participate for example, in Bristol Bright Night (the H2020 Researcher’s Night) and in Open Doors activities of the University of Bristol aimed to secondary schools. Dr. Rodriguez-Arco has also participated in PERFORM, a European Union Horizon 2020 research project investigating the use of innovative science education methods based on performing arts, in fostering young people’s motivations and engagement with STEM in selected secondary schools in France, Spain and the United Kingdom. She has also joined the Marie Curie Alumni Association joining courses (in Research Integrity, for example) and meetings
Our findings on phagocytosis-inspired behaviours in mixed populations of protocell droplets are a first step towards the engineering of synthetic protocell consortia capable of collective behaviour. In a wider perspective, our studies will contribute to the design and engineering of synthetic protocell ecosystems based on interacting networks of micro-compartmentalized colloidal objects with life-like properties such as phagocytosis, signalling, cooperation, specialization, endosymbiosis, predation and swarming.

In the particular case of artificial phagocytosis-like behaviour, we speculate that the controlled engulfment of a second population of droplets could be exploited in microfluidic technologies involving two-phase droplet micro-reactors. One of the difficulties of these systems is the controlled addition of a reagent into an existing droplet stream. This normally requires complicated microfluidic devices involving multiple injectors. Using a phagocytosis-like system will enable multistep and sequential delivery of reagents into a MPE droplet micro-reactor via colloidosome intake which can be coupled with magnetic-field directed assembly and guidance. This could have an impact on enzyme-mediated decontamination and biotransformation of waste oil pollutants for example.