Result, the first of its kind, could lead to a powerful new diagnostic tool in medicine
About four years ago, Arizona State University biophysicist Stuart Lindsay’s research team got a lab result that even he couldn’t quite believe. As with most scientific surprises, it goes against all conventional wisdom: the first evidence of a protein that could conduct electricity like a metal.
It’s a result that could have important implications in medical diagnostics, but they didn’t quite accept it at first.
After years of trying to disprove the results himself and trying to account for every potential wrong avenue or detour, Lindsay and his research group have published their new findings in the advanced online edition of the Institute of Physics journal Nano Futures.
“What this paper is mainly testing out are all the alternative explanations of our data, and ruling out all of the artifacts,” Lindsay said.
“Basically, we’ve eliminated all of those sources of 'I don’t believe this data' and we are still seeing this weird behavior of this huge protein conducting electricity. It’s still there and it’s beautiful.”
How it began
Lindsay has spent his career building new microscopes that have become the eyes of nanotechnology and next-generation, rapid and low-cost DNA and amino acid readers to make precision medicine more of a reality.
In the process, Lindsay’s research team has learned a thing or two about how single molecules behave when tethered between a pair of electrodes, which is the foundation for how his DNA readers work.
The technology, called recognition tunneling, threads single molecules down a nanopore like a thread through the eye of a needle.
As they go down the nano-rabbit hole, electrodes measure the electrical properties of these single DNA or amino acid molecules to determine their sequence identity.
Having spent a considerable amount of time building DNA and amino readers, they decided to give whole proteins a try.
“The thought was, that if you can specifically trap a whole protein between a pair of electrodes, you would have a label-free electronic reader,” said Lindsay, who serves as director of the Biodesign Institute’s Center for Single Molecule Biophysics and as Regents’ Professor with ASU’s Department of Physics and the School of Molecular Sciences.
The potential to have a nanotechnology device sensitive enough to identify a single protein molecule could become a powerful new diagnostic tool in medicine.
But the building blocks in every cell, proteins, were thought to behave electrically as inert organic blobs. Electronically, they were assumed to act as insulators, just like putting a piece of plastic over a metal wire.
“There is just a large amount of swept-under-the-rug data on the electrical properties of proteins,” Lindsay said. “There is one camp who dismiss these claims. There is another camp that says proteins are incredible electrical conductors. And never the twain shall meet, just like American politics.”
So four years ago, one of his graduate students at the time, Yanan Zhao, tethered a protein between two electrodes, turned up the voltage, and voila! The protein started performing like a metal, with a wild and “remarkably high electronic conductance.”
“If it’s true, it’s amazing,” Lindsay said.
Where the weirdness begins
The first remarkable results were performed with a technology Lindsay helped spearhead, called Scanning Tunnel Microscopy, or STM. A glue-like protein, called an integrin, that helps cells stick together and assemble into tissue and organs, was used in the experiment.
Extending from the tip of the STM was another electrode attached to a small molecule, called a ligand, which specifically binds to the integrin protein. Once held in place, the STM has a lever arm and probe much like a stylus and needle on a turntable to bring the ligand in contact with its integrin target.
This is where the weirdness began.