Molecular 'Wiretap' that Watches Human Protein Work for the First Time
CREDIT: University of California, Irvine
Proteins in the body digest food, fend off invading bacteria, make important hormones and chemicals, and much more. Yet because they’re so small, it’s difficult to learn exactly how they work—and learn how they might go wrong in diseases such as Alzheimer’s or cancer. Now, researchers at the University of California, Irvine, have created a way to wiretap single proteins, to listen in on what they do over several minutes or even several days.
The researchers attached a protein called a lysozyme, which is responsible for destroying bacteria, to a nano-sized transistor. Transistors are important components in any modern electronic device, including computers and cell phones, because they amplify electrical signals, the way bullhorns and microphones amplify sounds. This new transistor amplifies the signals that lysozymes transmitted as they grabbed bacteria and started breaking their chemical bonds.
“Our transistor circuit is acting like an electronic microphone, listening in to the motions and the chemistry of the protein,” said Philip Collins, a nanotechnology researcher who led the research. Collins and his colleagues published their results in the journal Science.
While many researchers have worked to build transistors that can detect single molecules, this is the first time anybody has built a transistor that can sense the subtle movements of a lysozyme doing its job. “This is special in that it actually measures activity,” said Taekjip Ha, a University of Illinois physicist who studies techniques for measuring molecules. “What they achieve here is much more difficult.”?Ha was not involved in creating the new transistor.
Often scientists use glowing, fluorescent dyes to observe what proteins are doing, but the glow only lasts a few seconds before fading. Using the new transistor, Collins’ team monitored a lysozyme for 10 minutes, said Gregory Weiss, a biologist and chemist at the University of California, Irvine, who worked with Collins on the project. They could probably watch the protein for a whole afternoon or several days, experts say. “There’s essentially no limit for how long they can watch a single enzyme,” Ha told InnovationNewsDaily.
The longer observation time let Weiss, Collins and their colleagues watch lysozymes hold onto enemy bacteria for long enough to break hundreds of chemical bonds in a row, creating long ruptures in the sides of the bacteria. They got to watch the proteins transition between working at high and low speeds. "That's something I’m really excited about," Weiss told InnovationNewsDaily. "If we can learn the rules for why it is that it goes slow and sometimes goes fast, then potentially, we could lock it into shapes that prevent it from going slow." They could make proteins that are more effective at killing bacteria for future drugs, he said.
Transistors are traditionally made of silicon, but the Irvine scientists chose to use carbon nanotubes because their small size ensures they’re sensitive enough to detect the signals that molecules generate. “The nanotube is the world's smallest wire,” Collins told InnovationNewsDaily. “That's perfect for wiring up to small objects like individual molecules."
Collins and Weiss are now using their transistor to study other proteins. Lysozymes were just the test protein—they were first isolated a century ago by the famed chemist Alexander Fleming, who collected them from his own tears. They are among the best-studied proteins in science.
The Irvine research team is now comparing healthy and diseased proteins to find what makes them different, Collins said. Ha said transistors that can measure the molecules of life would be useful as sensors for pathogens in food or changes in the atmosphere. “You can imagine deploying the device as a sensor everywhere,” he said. “This paper represents a very nice step.”