Like minute ants, Myosin V proteins can heft and haul things many times their own weight, much larger containers of chemicals, for example, that nerve cells need to fuel the electrical signals they fire.
But how the proteins move along cellular pathways with their loads has been a subject of biological debate. Did they crawl like an inch worm or did they, in effect, walk on two legs?
"That's been very controversial," said University of Illinois Professor Paul Selvin recently. "There have been results basically on both sides, but not definitive results because people basically didn't have the tools."
Now, Selvin, UI Professor Taekjip Ha and colleagues have developed the tools and answered the question, at least in the case of Myosin V. In a cover article in the journal Science this month, they say the proteins are walkers.
And they have pictures, sort of, to prove it – of movement by structures a thousand times smaller than a cell.
Selvin, a UI physics and biophysics professor, said the extremely accurate imaging technique developed by the researchers is about 20 times better at capturing the submicroscopic action than anything previously available .
"We have the hammer and there's a lot of nails out there we can hit," he said.
Indeed, there are hundreds of what Selvin called "molecular motors" – more than a dozen types of Myosin alone – that convert chemical energy to mechanical motion like Myosin V. They're involved in many key biological processes scientists want to understand on both basic and applied levels.
Myosin V itself is prevalent in the brain. Problems with it there contribute to seizures and other neurological disorders.
It also moves pigmentation granules in the skin. You don't get a sun tan without it, and if it's defective you suffer pigmentary disorders.
A relative, Myosin II, is important in all kinds of muscle movement, including the beating of the heart.
Myosin also plays a role in cell division, a process that, when it goes awry, is literally a cancer.
"The hope is that the basic research will ultimately translate into new drugs, clinical procedures," Selvin said.
Understanding how the proteins work also could be useful in nanotechnology, where researchers are trying to mimic the natural molecular motors with tiny man-made versions billionths of a meter in size, for uses ranging from more powerful computer chips to drug delivery.
Selvin said the imaging technique developed by the UI scientists also could be applicable in genomics, for instance as researchers use fluorescence to pinpoint the location of gene mutations linked to many diseases.
"It looks like this technology will probably be useful even beyond molecular motors," Selvin said. "If you want to track any moving molecule, this may be useful."
The researchers, including UI graduate students Ahmet Yildiz and Sean McKinney, built on a method of attaching fluorescent dye to the proteins' "feet," developed by University of Pennsylvania scientists Yale Goldman and Joseph Forkey.
The dye is then illuminated with a laser, in essence causing it to glow, and used to track the proteins' movement.
The UI researchers place the tagged proteins on a slide coated with Actin, another protein that acts as a highway for Myosin inside cells, feed them a little chemical fuel and watch them go.
A sensitive digital camera and microscope array captures the miniscule light emitted by the dye, showing how the position of the proteins changes over time – in effect measuring their 74-nanometer stride, 10 million times smaller than ours – and proving they walk rather than crawl.
Ha, a UI physics professor, found a way to make the dye fluoresce longer, instead of burning out quickly, a key development because it allowed the researchers to capture a series of images tracking the movement of the proteins.
Selvin said they also benefited from recent advances in the camera technology.
"These supersensitive cameras are relatively new," he said. "They're only a few years old."
The research was funded by the National Institutes of Health, the National Science Foundation, the U.S. Department of Energy and the Carver Trust.
You can reach Greg Kline at (217) 351-5215 or via e-mail at email@example.com.