LIVING and non-living components have been combined using microfluidics to create a hybrid cell capable of using a biological cell to process chemicals.
Biological cells can perform extremely complex functions compared to artificial cells, but artificial cells can have user-defined properties, and combining the two could have great advantages, particularly for medicine. A team at Imperial College London has successfully demonstrated a method for combining biological and artificial cells into a functioning hybrid. While biological components such as enzymes have been encapsulated previously, this is the first time that a whole biological cell has been used.
Microfluidics was used to create droplets of a defined size containing biological cells and enzymes. The droplets then acted as templates around which the artificial vesicles were assembled. Despite the mechanical sheer forces associated with droplet generation, the cells remained active.
The hybrid cell was constructed so that the vesicle host creates a shell around the biological cell. The biological cell has an organelle-like function and can process chemical feedstocks inside the vesicle. The researchers demonstrated the ability of the hybrid cell through a reaction sequence of three steps: hydrolysis of the lactose feedstock by the biological cell produces galactose, the galactose product is oxidised to produce H2O2, and then oxidation of a fluorogenic molecule by H2O2 in the presence of an enzyme produces the fluorescent end product, resorufin.
Using a reaction process that culminates in fluorescence allowed the researchers to see if the hybrid cell was functioning. Over three hours, the fluorescence increased significantly in the hybrid cells, whereas a control sample without a biological cell within the vesicle showed hardly any signs of fluorescence. The vesicles of the hybrid cells also remained intact a week later and still successfully held the encapsulated biological cell.
The artificial shell also acts as a shield to protect the biological cell from the local environment, and this was tested by exposing the hybrid cells to a solution of copper, which is toxic to biological cells. By monitoring the fluorescence, the researchers observed that 66% of the cells were still viable after two hours, compared to 6% in the control sample. The cell damage that did occur wasn’t due to copper penetrating the shell, but was most likely the result of a build-up of waste products within the cells. This could be solved in future experiments by adding a protein that can expel waste without letting the copper through the shell. Protecting the biological cell with a synthetic one has important implications in healthcare, as such a system could be used to prevent the body’s immune system from attacking the biological cell.
“The system we designed is controllable and customisable,” said Yuval Elani, first author of the study. “You can create different sizes of artificial cells in a reproducible manner, and there is the potential to add in all kinds of cell machinery, such as chloroplasts for performing photosynthesis or engineered microbes that act as sensors."
Future work will involve engineering the artificial shell to act more like a membrane that can be programmed to open and release chemicals in response to specific signals. This could be used to deliver drugs to certain areas of the body, and could help to reduce side effects in cancer treatments by only releasing drugs at the site of a tumour.
Scientific Reports http://doi.org/cmpb
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