Tiny molecular motors that can haul cargo thousands of times their weight with energy efficiencies that put man-made machines to shame. The stuff of science fiction? Not at all. Inside every one of your cells are nature's versions of these little engines.
As reported in the June 27, 2003, Science magazine, scientists at the University of Illinois, in collaboration with colleagues at the University of Pennsylvania, have taken one step towards understanding how these biomolecular motors move. It's known that these motors, made of proteins, take miniscule steps—about 10–100 nm. That's a thousand times smaller than the width of a human hair, and about 10 to 100 million times smaller than the size of your gait. But how do these little motors take a step? For example, a human adult moves by walking—putting one foot in front of another. A baby moves by crawling, not so different from how an inchworm travels, keeping one part always in the lead and dragging the rear behind.
Graduate student Ahmet Yildiz, working in Professor Paul Selvin's laboratory in the Department of Physics department at the University of Illinois, found that at least one biomolecular motor moves by walking, not inchworming. Amazingly, these tiny motors, which have two "legs" and a "body", appear to walk much as we do.
The scientists zeroed in on one particular protein motor called myosin V. It's found in almost all cells in your body, but is particularly prevalent in nerves and is also found in skin, where it moves little pigment granules. Defects in this protein lead to neurological problems, including seizures, and pigmentation problems. Four years ago scientists at Stanford, Yale, and the University of North Carolina found that the cargo moved about 37 nanometers for each step that the myosin took. They made this measurement by attaching a large bead to the motor and watching it move. The bead, or cargo, sits at the top of the myosin molecule, much like your head is attached to the top of your body. But their measurement still didn't answer how the myosin moved—by walking or by crawling. To do this, scientists had to look at the feet and legs of the motor.
Selvin's group teamed up with Professor Yale Goldman and his post-doc, Joe Forkey, at Penn's Pennsylvania Muscle Institute, who had already isolated myosin V and attached a fluorescent dye to one of its legs. "We've developed a technique that enables us to measure these miniscule steps and watch how each leg moves, one molecule at a time" says Selvin. The technique, developed with graduate student Sean McKinney and Professor Taekjip Ha, also in the Department of Physics at Illinois, used a digital camera attached to a microscope sensitive enough to see the faint glow of a single emitting dye molecule. To apply it to myosin, they stuck labeled myosin down on a slide coated with actin, another protein that acts as a highway for myosin to move on. "We fed the myosin some chemical food and watched it go," says Selvin. The initial stumbling block was being able to see the miniscule step coming from a single, relatively dim dye molecule on the myosin. But by coaxing the dye to emit enough photons, they managed to precisely locate the position of the dye to within about a nanometer, or one-billionth of a meter. They measured the step size by taking a picture of where the dye was just before, and just after, a step.
When the dye was near the rear foot, they found the dye moved 74 nm—twice the cargo step size—and when on the front foot, it didn't move at all. This motion is exactly what was expected if the myosin V walked. For example, when you walk, your back foot moves forward twice the distance that your head moves, while your front foot simply pivots, staying in one place. In contrast, in an inchworm or crawling motion, all parts of your body move forward the same amount during a single step. "It's amazing," says Selvin, "that inside each of your cells are tiny, tiny creatures, literally walking around, keeping you alive."
But this is just the beginning. There are hundreds of different types of biomolecular motors, involved in everything from muscle contraction, to moving chromosomes during cell division, to reloading necessary ammunition within nerves cells so they can repeatedly fire. The cell is a busy place, much like a city where things are constantly bustling around. "It will be interesting to see whether all motors move in the same way," says Selvin.
The Illinois work was supported in part by the National Institutes of Health, the National Science Foundation, the U.S. Department of Energy, and the Roy J. Carver Charitable Trust. Any opinion, findings, and conclusions, or recommendations expressed herein are those of the authors and do not necessarily reflect the views of the funding agencies.