WINGING IT. This tiny engine is based on a single molecule of ATPase bonded to a propeller made from protein. It spins at the rate of 3 to 4 revolutions per second.

This crude structure is, in fact, a motor. And like young Henry Ford's first Model-Ts, it may be a harbinger of an equally significant industrial revolution--this time, on the scale of billionths of a meter. Created by biological engineers at Cornell University, it makes a reality out of what seemed a purely theoretical idea just a couple of years ago: building machines on a molecular scale.

By comparison, the miniscule gears and wheels that have been etched from silicon using a process called micromachining are behemoths. But self-propelled devices powered by molecule-size engines could function not just inside the body, but literally inside individual cells. To build this micro powerplant, the researchers, headed by Carlo Montemagno, turned not to silicon, but to nature, and combined the organic with the inorganic.

Living cells, too, have engines, such as those that wave bacterial cilia or transport energy across membranes. The scientists found their molecular stator and rotor in the form of an ubiquitous molecule, the enzyme ATPase. The ATPase molecular motors occur on the membranes of mitochondria, microscopic bodies in the cells of nearly all living organisms, as well as in chloroplasts of plant cells; within these organelles, the enzyme is responsible for converting food to usable energy.

POTENT ENGINE. The ATPase motor (top) is built on the membranes of cellular mitochondria. The force it generates in moving energy in cells places it among the most powerful of any known molecular motors.

The moving part of ATPase is a central protein shaft (or rotor, in electric-motor terms), less than 12 nanometers in diameter, that rotates in response to electrochemical reactions with each of the molecule's three proton channels (comparable to the electromagnets in the stator coil of an electric motor). ATP (adenosine triphosphate) is the fuel for the molecular motor's motion. Energy becomes available when atomic bonds between phosphate atoms are broken during hydrolysis, converting ATP into ADP (adenosine diphosphate). During hydrolysis, the shaft rotates in a counterclockwise direction, whereas it rotates clockwise during ATP synthesis from ADP.

To fashion ATPase into a motor capable of mechanical work, Montemagno, an assistant professor of agricultural and biological engineering, turned to genetic engineering. He produced the ATPase molecules using Escherichia coli bacteria that were altered to include a gene sequence for ATPase from the thermophilic bacterium Bacillus PS3.

He then separated the molecules from the cell membrane and attached them to a metallic substrate using a synthetic peptide composed of histidine and other amino acids. These histidine peptides, like little "legs," tied the molecular motors to the substrates, nanofabricated patterns of gold, copper or nickel--the three standard contact materials in integrated circuits that might one day provide control systems for the motors. Of the three metals, nickel showed the greatest adhesion.

Next, the researchers bonded propeller-like filaments made from polymerized proteins to the top of the motor shaft. With further genetic manipulation, the Cornell engineers expect E. coli to turn out ATPase molecules with tiny propellers built right in--making each a kind of nano-motorboat. The protein "props," ranging from 0.5 to 8 microns long, were made of a material that would fluoresce under certain wavelengths of laser light so their motion could be viewed.

MOTOR MOUNT. The ATPase motor is attached to a nanofabricated nickel substrate by "legs" (green) of a synthetic peptide. This connection may allow engineers to integrate nanoengines with the logic of integrated circuits.

Indeed, observing the motion of anything so tiny requires almost as much technology as it does to create it in the first place. In recent experiments, the Cornell engineers tagged the ATPase molecule's rotor with giant fluorescent microspheres, measuring 1 micron (1 millionth of a meter) in diameter. They could then observe the microsphere's movement using a differential interferometer and a charge-coupled device kinetics camera.

When the scientists switched on their motor--by bathing it in a solution of ATP--the rotor spun for 40 minutes at 3 to 4 revolutions per second, the group reports in the September issue of the journal Nanotechnology.

Still, it won't be any day soon when tiny "smart" devices are swimming through the body, dispensing drugs to kill cancer cells. "We have succeeded in establishing biological and nanofabrication platforms for the production of organic/inorganic hybrid nanoelectromechanical systems (NEMS)," says Montemagno. "But we have a long way to go before it's safe to turn these little machines loose in the human body." Issues such as the impact of waste products, including heat and protons, on the motors' performance and their surrounding environment, must be addressed.

But it's possible that, far sooner, these nanoengines will be pumping fluids, opening and closing valves and providing mechanical drives for a new class of nanomechanical devices. "For a technology that wasn't expected to produce a useful device before the year 2050, I think we've made a pretty good start," says Montemagno.

Images: Cornell University