Nature uses tiny nano-machines that could work miracles if we learn how to build them
By Karl Leif Bates
The Nobel Prize-winning physicist Richard Feynman of the California Institute of Technology closed his visionary 1959 talk on the potential of nanotechnology, "There's Plenty of Room at the Bottom," by offering a prize to the first person "who makes a motor which can be controlled from the outside and, not counting the lead-in wires, is only a 1/64 th-inch cube." That's half the thickness of a credit card.
What Feynman didn't realize at the time, and couldn't have known, was that he was already in possession of trillions of devices far smaller and more powerful than he imagined. To utter this challenge and to gesticulate as he spoke, Professor Feynman was relying on the molecular motors and machines that worked within almost every cell throughout his body. Some of them are 20,000 times smaller than the device he imagined and far more efficient than anything our species has ever built.
Biology has been using these little machines and motors to operate living cells for millions of years: in bacteria that swim by spinning their hairlike propeller; in the little levers that pull our muscle fibers tight; and in even smaller rotary motors on the surface of mammalian cells that turn in response to a single proton of electrical current.
So, before Feynman even thought of it, nature had nanotechnology nailed.
Rather than starting from scratch to invent Feynman's nano-motor, scientists and engineers at the University of Michigan are looking at these self-assembled, ultra-efficient, incredibly small, natural motors that exist all around us and within us. The blueprints and operating instructions for them are contained within DNA.
"These things are machines!" says Michael Mayer, an assistant professor of chemical and biomedical engineering. "It would be amazing to figure out how to make them."
Like a tiny longshoreman
His colleague, Edgar Meyhöfer, an associate professor of mechanical and biomedical engineering, is particularly interested in a 50-nanometer long machine called a kinesin (ky-nee-sin). This molecule is like a longshoreman walking across the inter-cellular space carrying cargo on its shoulders. One end of the dumbbell-shaped molecule is anchored to a vesicle, a little cargo container within the cell. The other end walks along a length of tube-like material called a microtubule.
The kinesin molecule will make precisely one 8-nanonometer step in response to one molecule of ATP (adenosine triphosphate), the universal fuel of cells. Click-click-click, it moves along the microtubule in step-wise fashion carrying its cargo, as long as it keeps getting ATP. "Every plant and animal has kinesins." Meyhöfer says. "They are ubiquitous."
Human pathogens have been found to hitch rides around the interior of the host cell on kinesin molecules. The vaccinia virus that causes relatively harmless cowpox and gives us the word vaccine makes its way across the cell in under a minute riding atop a kinesin—a trip that would take more than 10 hours by simple diffusion.
Other infectious agents are suspected of performing the same trick. Interruption of this process might become a new target for anti-bacterial and anti-viral therapies.
Not only is it tiny, kinesin's motor is about 50 percent efficient, which is about twice as good as a gasoline engine. And pound for pound, kinesin produces nearly 15 times more power than that man-made engine.
Meyhöfer and Alan Hunt, an assistant professor of biomedical engineering and gerontology, are experimenting with anchoring kinesins on a firm platform like a sheet of glass and allowing them to shuttle microtubules around overhead. Attach something bigger to the microtubules and you've got a nano-motor or a nano-conveyer belt for a microchip machine.
Hunt shows a black and white movie on his computer monitor. White worm-like shapes are careening around a black space, pretty much at random. Hunt explains that these are pieces of microtubule being shuttled around by a forest of excited kinesins mounted to a piece of glass.
"We would like to be able to put a single molecule into a location and know that it is working," says Meyhöfer. "That is truly nanotechnology."
This collaborative project spans disciplines, and so it also involves collaboration with assistant professors Joe Bull of Department of Biomedical Engineering, Ernest Hasselbrink and Katsuo Kurabayashi of Mechanical Engineering, and Lingjie "Jay" Guo of Electrical Engineering.
"One of the limiting factors in MEMS (microchip machines) is a lack of good motors," Hunt says. But these remarkable little machines may do the trick. Hunt's lab has been able to bind kinesin motors to a hard surface in very tight, uniform patterns, and they function perfectly.
Meyhöfer says it also is possible to make a working kinesin even smaller. If you clip out the middle part, it will still work. "I think you could easily fit the whole machine into a 10 nanometer cube." (If this motor were one-inch long, Feynman's motor would be more than half a mile.)
When nanotech is able to make the gears, drive shafts and levers needed by the MEMS devices, they won't be purely mechanical and they won't be hard like silicon. The nanotech parts of these machines will be floppy, more like balloon animals than precision-milled steel. And their actions will be temperature sensitive, more like chemistry.
"At the nano-scale, you cannot separate physics from chemistry from biology, because they are all entwined," Hunt says.
The smallest muscle
The molecular motor that moves our muscles is called myosin , and it looks sort of like a two-legged bug. A molecule of ATP fuel produces one "stroke" of the myosin leg, like a single stroke of a rowing machine. Each stroke produces 3 to 10 piconewtons of power.
"A piconewton is about the gravitational attraction between me and this pen," Hunt says, holding up a dry-erase marker. "Or it's about the pressure exerted by shining a flashlight on a penny."
In fact, the gentle force exerted by light is what Hunt and Meyhöfer use to measure the miniscule power of a single molecular motor. They have one end of a molecule hold on to a tiny plastic bead that is fixed in a cone of tightly focused laser light. Then they pull the bead away "like a spring attached to the wall" and watch how the molecule pulls back against the drag created by the light. The pull of kinesin, for example, is just 4 to 6 piconewtons.
Individually, these motors may not seem like much, acknowledges Meyhöfer, whose doctorate is in zoology. But put millions of myosin motors together in series and in parallel and you have the muscle power that enables 4-foot-11-inch, 123-pound Olympian Halil Mutlu of Turkey to lift 350 pounds over his head.
The cell's dynamo
Though it's not a primary focus of his work, Michael Mayer, who trained in chemistry and biophysics, is also intrigued by a 20-nanometer motor called ATP synthase. It's a little rotary motor in the membrane of mitochondria (the cell's power house) that turns in response to incoming protons. Rotation of the motor converts adenosine diphosphate (ADP) molecules into ATP molecules, the cell's fuel.
The ATP-making motor is more than 75 percent efficient, and its design is ancient, appearing in just about every form of life, except for archaea, the forerunners of modern bacteria. It is also constructed to run backwards, a trick some bacteria use to spit out protons in response to ATP.
Chemist Ioan Andricioaei takes his telephone off the hook. "This cord is like a DNA helix," he says, spinning the handset to twist the cord until it's a snarled mess. "You have twists on top of twists now, which also happens in DNA."
But in order for the cellular machinery to read the DNA's crucial genetic information, it has to be more relaxed, so that the spiral molecule can open up. "What would be your strategy for undoing this?"
If it's a phone cord, you can unclip one end and let it relax.
"Exactly!" Andricioaei says. "Nature does the same thing."
The tiny motor that accomplishes the untangling is an enzyme called topoisomerase (toe-po-EYE-so-mare-ays), and its shape resembles a tiny PacMan. The topoisomerase molecule binds to the side of the twisted helix, clips an opening in one of the two spiraling backbones of the DNA, and then lets the thing unwind itself. Once the DNA has relaxed, the enzyme repairs the clipped backbone and goes on its way to find another snarl to work on.
Andricioaei's team is building computer models of a small area of the genome, about 100 angstroms (0.1 nanometer), in which the topoisomerase is at work to see it in motion. Understanding topoisomerase better could lead to cancer drugs that prevent the cancer cell from duplicating itself, Andricioaei says.
The little engine that could
The most efficient, powerful nanomotor found in nature so far is a proton-fueled rotary motor that bacteria use to swim. This motor spins the base of each hair-like flagellum on the bacterium, making the hair into a long propeller.
A single flagellar motor puts out about 20 piconewtons of torque, speeding the bug forward at about 1 micron per second. Its power is stunning: 13,600 watts per kilogram, about 45 times the output of a gasoline engine.
This exquisite little engine could put a great spin on the nanotechnology devices of the future. Learning how to build and operate these machines would lead to the ultimate interface of man and machine.