Schrödinger's protein is both a conductor and an insulator

Researchers at Arizona State University (ASU) have uncovered the first evidence of a protein that can conduct electricity like a metal — so long as the voltage is high enough.

The discovery was helmed by Professor Stuart Lindsay, who has spent his career building microscopes for nanotechnology and DNA-reading applications. In the process, he and his team have learned 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 tunnelling, threads single molecules down a nanopore like a thread through the eye of a needle. As they are threaded, 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, Professor Lindsay decided to move on to whole proteins. “The technological goal here was, can we use our technology to electronically detect whole proteins?” he said.

He and his team ended up using their recognition tunnelling to measure the electrical conductance of intact proteins, the idea being that “if you can specifically trap a whole protein between a pair of electrodes, you would have a label-free electronic reader”, Professor Lindsay said. And a nanotechnology device sensitive enough to identify a single protein molecule could become a powerful new diagnostic tool in medicine.

The test was opening up a can of worms, as there was a lot of unclear data about the electrical properties of proteins. Some scientists believed they acted as insulators, like putting a piece of plastic over a metal wire. According to others, proteins are incredible electrical conductors.

Professor Lindsay’s then graduate student Yanan Zhao decided to resolve the situation once and for all, tethering a protein between two electrodes and turning up the voltage. Almost instantly, the protein started performing like a metal, exhibiting what has been described as a wild and remarkably high electronic conductance.

Now, after four years of trying to disprove the results of the experiment, the researchers have published their findings — as well as their theories — in the journal Nano Futures. As noted by Professor Lindsay, “What this paper is mainly testing out are all the alternative explanations of our data, and ruling out all of the artefacts.”

The initial results were captured with a technology Professor Lindsay helped spearhead, called scanning tunnel microscopy (STM). The experiment utilised a glue-like protein, called an integrin, that helps cells stick together and assemble into tissue and organs.

Extending from the tip of the scanning tunnel microscope 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.

According to Professor Lindsay, the researchers observed “giant pulses of current when the probe was known to be a great distance from the surface” — too great a distance for the electricity to flow through by electron hopping, or tunnelling, as occurs with Professor Lindsay’s recognition tunnelling sequencing technology. Professor Lindsay spent several years searching for an explanation, to no avail — until he came across a paper by theoretical biophysicist Gabor Vattay at Eötvös Loránd University, Budapest, which “involved some absolutely amazing quantum mechanics”, he said.

“It turns out that energy level spacings in a quantum system signal whether the system is a conductor or insulator,” Professor Lindsay said. “There is a special signature of a state poised between conducting and insulating, and Gabor Vattay looked at a bunch of proteins, finding them poised at this critical (and highly improbable) point.”

Vattay’s theory suggests that an electrical fluctuation can kick-start a protein into being a great conductor or a great insulator, which matched the results of Professor Lindsay’s experiments. “We were seeing this weird behaviour in this huge protein conducting electricity, but it is not static,” he said. “It’s a dynamic thing.”

Professor Lindsay added that these electronic spikes occurred with increasing frequency as the researchers upped the voltage across the protein. “Below a certain bias, it’s just an insulator, but when the fluctuations start kicking in, they are huge,” he said.

Professor Lindsay got in touch with Vattay, who subsequently used some of the best supercomputers in Europe to analyse the team’s protein. As explained by Professor Lindsay, “There are three curves for the distribution of energy level spacings: one corresponding to a metallic state, another to an insulator state, and middle third, corresponding to the quantum critical state.

“Low and behold, our protein is in the quantum critical state, if you believe the theory.”

The research team went on to manufacture a nanodevice to more finely control another series of experiments, with a carefully sized gap to control the protein and the amount of voltage that can be applied to it. This made a big change from previous experiments, where they didn’t know precisely what was going on at the tip of the STM.

“In the device, you get this beautiful switching on and off of the electrical conductance of the protein,” Professor Lindsay said.

The researchers’ results demonstrate the fundamental quantum forces being enacted on the integrin protein during the experiments. They are also upending the way scientists are viewing the electrical properties of proteins, with Professor Lindsay stating, “There are people who are beginning to think of proteins as quantum mechanical objects.”

Professor Lindsay now wants to explore other medically important proteins and measure their behaviour using the solid-state nanodevices, in the hope that he will learn whether these other proteins turn out to behave like metals or insulators.

“I believe the data now,” he noted, “but it’s only one protein so far.”

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