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Phil Collins develops tiny wire 'bugs' to study molecular behavior

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Phil Collins, professor of physics and astronomy at the University of California at Irvine, stands with a vacuum chamber in his lab. The chamber cools transistors, a process that reveals quantum properties. (Photo: Rebecca Fairley Raney)

Long before the nanotech frenzy kicked in, AAAS Fellow Phil Collins was thinking about studying "tiny wires." Now, 30 years after he started toying with the idea, the rise of nanotechnology is creating novel research partnerships, as biologists, engineers—and physicists—seize on its vast possibilities for molecular research.

Collins, a professor of physics and astronomy at the University of California at Irvine, is helping researchers collect better observations of how molecules work by attaching wires to them that are 1 nanometer in diameter.

In this work, Collins said, success depends on using the smallest possible wires. "When a molecule moves by a couple of angstroms," Collins said, \we can hear it.\" 

It's a novel method of studying enzymes that may lead to better medical treatments.

This area of research emerged from a series of small discoveries Collins made over the course of decades.

Collins was first interested in these concepts in the 1980s. He was studying physics and electronics as an undergraduate at the Massachusetts Institute of Technology, and he described this interest to his adviser. To him, it sounded like "an exciting intersection between two fields."

His adviser did not encourage him. "He said, 'You have to pick a field,' " Collins said. " 'What you described is not a field.' "

In the 1990s, new tools such as scanning microscopes and electron microscopes made their way into labs. As a result, scientists were able to develop tools to make nanoscale materials, and they were able to see them and study their properties.

Collins started thinking about creating nanocircuits during graduate school at the University of California at Berkeley in the 1990s. At Berkeley, researchers were working with the tiny wires, and they found that "they did conduct, but they didn't have the right values," Collins said.

More importantly, he said, \"the value changed according to environment." In fact, they were hypersensitive to environmental changes, and Collins suspected that this sensitivity went all the way to the molecular level.

He was right.

Through a series of small projects in the past 15 years, he developed a reliable method of using tiny wires to study molecules. In 2004, he started working with AAAS Fellow Gregory Weiss, a professor of chemistry at UCI who had been thinking about attaching viruses to electronics. Collins provided the nanotubes for the research, and Weiss provided the molecules.

"It sounds like science fiction even to scientists," Weiss said. But these methods are producing surprising discoveries about the behavior of molecules, he said. "This is having a real impact in biology."

Collins compared the process of creating nanocircuits to placing a microphone on a molecule. "It's like bugging a phone or bugging an office," he said. "We can bug the tail of a protein."

And he can do it without changing the molecule's behavior. The wire essentially brings a signal from the molecule out to the world for observation.

"We're watching molecules in action," Collins said.

A recent discovery involved the behavior of the enzyme lysozyme, which Collins has unofficially dubbed the "Pac-Man molecule," because of its propensity to systematically chomp through bacteria. Lysozyme resides in large concentrations in human tears and probably prevents eye infections.

Using conventional methods, researchers have been able to watch the enzyme operate for short periods of time. When Collins' team attached a wire to the molecule, they were able to watch it for two weeks. Weiss said that it's like watching a race car run a course all day instead of just for a couple of laps.

The enzyme makes a sound when it chomps on a molecule. When it gets food, the molecule clicks away like someone snapping his fingers.

By learning more about how molecules operate, Weiss said, \"this type of research can guide us to develop more effective pharmaceuticals in the future."

The Collins lab has also studied the enzyme polymerase, which builds DNA strands and double checks them for errors, as well as the enzyme kinase, which sits inside cells walls and switches chemicals on and off. Collins marvels at the things he has seen—or rather, heard—some molecules do.

"A single molecule varies from second to second more than anyone expected," he said. "One molecule can turn lots of things on or off. It does a thousand different things."

What to do with this knowledge is another matter, which Collins compared to finding an alien spaceship in the back yard.

"You can take it apart," he said, \"but you don't know what to do with it."

 

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Phil Collins, professor of physics and astronomy at the University of California at Irvine, stands with a vacuum chamber in his lab. The chamber cools transistors, a process that reveals quantum properties. (Photo: Rebecca Fairley Raney)
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