The dream of controlling biological cells electronically isn't just for sci-fi writers – if we can achieve it, scientists believe it will revolutionize the fight against disease. And now we may be a step closer - researchers from the University of Maryland (UM) have created an electrogenetic "switching" system in bacterial cells that lets them influence the way the single-celled organisms behave.
The challenge in creating a bioelectric hybrid system is that the two systems operate so completely differently.
The cells that make up all living things typically respond and signal to other cells through molecular signals. Through a process called gene expression, the information stored in each cell's DNA is converted into instructions for actions by creating molecules such as proteins, enzymes and hormones.
Microelectronic systems, by contrast, communicate via electrons, usually generated by an energy source.
Although there's no way electrons can flow freely within a biological system like electricity through a wire, there is a small class of molecules in most cells that stably shuttle electrons. These are called "redox" biomolecules – they can "hand off" electrons when they undergo reduction or oxidation reactions.
With minimal rewiring, the team was able to modify redox molecules to respond to electrons from the electrode of a patent-pending microelectronic device. The device could toggle the molecule's oxidation state to either an oxidized state where it would lose an electron, or a reduced state where it would gain an electron, essentially turning the redox molecules on and off.
They were then able to manipulate the bacteria to respond to the redox molecules "on/off" state by activating specific gene expressions.
This effectively created an electrogenetic switch that could turn parts of the bacteria "on" or "off" when voltage was applied.
In one example, the researchers were able to engineer a bacterial cell to turn the cell "on" so it would synthesize a protein that emits a fluorescent green hue, and "off" so it would stop synthesizing the protein. The cell would literally "light up" when it was switched on.
In another example, the researchers applied the method to bacteria that express a protein called CheZ that controls its swimming activity. The scientists could turn the part of the cell that synthesized Chez on and off, controlling whether the bacteria moved forward or not.
They also applied the method to bacterial cells that contain a natural biological signaling molecule that diffuses to neighboring cells, causing changes in the collective behavior of a whole community of bacteria. Using their device, the researchers could electrically program the group to repeatedly cycle the programmed behavior.
This new research ties into previous work by the University of Maryland where researchers found ways to "record" biological information by sensing the biological environment, and based on the prevailing conditions, "write" electrons to devices. Through these electrochemical devices, researchers were able to identify pathogens, and even monitor signs of stress in the blood levels of people with schizophrenia. In light of this previous research, the new study could potentially allow bacteria to be electronically programmed to deliver therapeutics to a specific site to help resolve such health problems.
"For example, imagine swallowing a small microelectronic capsule that could record the presence of a pathogen in your GI tract and also contain living bacterial factories that could make an antimicrobial or other therapy – all in a programmable autonomous system," posited William Bentley in an article about the research. Bentley is director of the Robert E. Fischell Institute for Biomedical Devices at UM.
"Electronics have transformed the way we live our lives, and there have been increasing efforts to 'connect' devices to biology, such as with glucometers or fitness trackers that access biological information," added UM research team member professor Gregory Payne. "But, there are far fewer examples of electronics communicating in the other direction to provide the cues that guide biological responses. Such capabilities could offer the potential to apply devices to better fight diseases such as cancer or to guide inflammatory responses to promote wound healing."
The results of the research have been published in the journal Nature.
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