Scientists in the US have developed electrical protein switches triggered by chemicals that can be used to control the flow of electrons within cells, a development which could facilitate next-generation bioelectronics and lead to the creation of smart pills that release medications only on demand.
The scientists at Rice University in Houston used E coli bacteria as a platform to test the protein switches. The metal-containing proteins that are expressed within cells upon the introduction of one chemical are functionally activated by another chemical.
If the proteins have been placed in the cell, they can simply be turned on and off.
"This is not a metaphor for a switch, it is a literal electrical switch built from a protein," said synthetic biologist Joff Silberg.
The proteins could facilitate next-generation bioelectronics, including complete biological circuits within cells that mimic their electronic counterparts.
The possible applications include living sensors, electronically controlled metabolic pathways for chemical synthesis and active pills that sense their environment and release drugs only when needed.
"Biology is really good at sensing molecules. That's an amazing thing. Think about how complex the cell is, and how proteins evolve that can respond to a single prompt in a sea of information. We want to leverage that exquisite ability to build more elaborate biomolecules and use these to develop useful synthetic biology technologies," said Silberg, a professor of biosciences and bioengineering.
"Natural proteins that move electrons more or less act as wires that are always there," said Biology graduate student and lead author Josh Atkinson.
"If we can turn these pathways on and off, we can make cells operate more efficiently," Atkinson said in a statement.
The metalloprotein switches - so called for their iron content - are quick. Nature typically controls electron flow by using genetic mechanisms to control the production of the protein "wires", Silberg said.
"It's all transcriptional. Even in a fast-growing E coli bacteria, it takes many minutes. By contrast, protein switches function on a time scale of seconds," he said.
To make the switch - which they use in a synthetic electron transfer pathway - the researchers needed a stable protein that could be reliably split along its peptide backbone to allow for the insertion of protein fragments that complete or break the circuit.
They based the switch on ferredoxin, a common iron-sulfur protein that mediates electron transfer in all the domains of life.
Silberg said the discovery should lead to custom-designed switches for many applications, including contact with external electronic devices.
"It's why we've been so gung-ho about this idea of bioelectronics, a whole field that's emerging as synthetic biology gets more control over the design. Once you can standardise this, there are all kinds of things we can build with cells," he said.
That could include smart pills that release medications only on demand, or gut biome detectors that report on conditions. Or perhaps electrical circuits contained entirely within cells, he said.
"We can already map a lot of what electrical engineers do with capacitors and resistors onto metabolism, but until now, there have been no switches," Silberg said.
He suggested multiple switches could also turn a cell into a biological processor.
"Then we could see digital parallel processing in the cell. It changes the way we look at biology," Silberg said.
The work appeared in the journal Nature Chemical Biology.
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