Cell machinery grown in the lab causes real cells to recognize and respond to external cues

Imperial researchers have programmed bacterial cells to respond to changes in light and temperature using synthetic cell machinery.

The innovation is an advance for the field of cell engineering – a discipline working to transform and harness the power of biological cells for potential applications in medicine, biomanufacturing and biosensing.

Like the organs in our body, living cells contain substructures called organelles—cellular machines that perform specific tasks. In this research, scientists at Imperial College London developed artificial organelles before coupling them to bacterial cells to coax them to recognize and respond to external cues. They designed the organelles to “translate” external signals, such as light and heat, into a chemical “language” that bacteria understand and respond to by producing proteins.

The lead author Dr. Yuval Elani from the Department of Chemical Engineering says: “With our artificial organelles, we got bacteria to respond to signals that they normally do not respond to. It’s like adding a little code to a cell giving it new functionality.”

The research could pave the way for potential applications in medicine by enabling artificially programmed cells to recognize diseased ones. Cells could also be programmed to produce and release drugs upon contact with diseased cells.

Programmable cells can also help in biotechnology, where they could make materials like medicines, proteins for food production, and industrial materials like plastics and detergents.

First author of the study Ph.D. Researcher Ignacio Gispert from the Department of Chemical Engineering says: “Giving cells new functions by incorporating artificial organelles is a completely new approach in cell engineering. Our artificial organelles are programmable modules that convert physical inputs into chemical signals.

“By demonstrating the feasibility of our new approach, we have opened a new route to cells that can be externally controlled if required.”

The results are published in Proceedings of the National Academy of Sciences (PNAS).

The power of the cells

In the cell engineering discipline of synthetic biology, scientists design artificial cells and organelles to mimic the shape and function of biological cells. One of the major challenges in this field is the development of “non-living” artificial cells to communicate with their biological “living” counterparts.

Researchers are now investigating how to translate their findings into next-generation therapeutics for diseases.

A goal in the field of cell engineering is to create fully programmable cells that can directly sense disease states or external cues administered by a physician. For example, these cells could sense elevated temperatures in tumors or respond to external light by illuminating diseased areas.

Another goal is for the cells to respond to these signals. This could be done by producing and releasing a drug that specifically targets such diseased cells and works only for the duration of exposure.

co-author dr. James Hindley of the Imperial Department of Chemistry says: “Although we do not demonstrate these applications directly, our research combines the programmability of tailor-made artificial cells with the performance of biological cells. This opens up a whole new avenue of potential to underpin future applications in medicine and biotechnology.”