Researchers Develop Chemical Switch to Control Biomolecular Motor

UCLA researchers at the Henry Samueli School of Engineering and Applied Science have created a tiny motor that they can turn on and off at will, bringing scientists one step closer to using such devices to repair cellular damage, manufacture medicines and attack cancer cells.

Writing in this month’s issue of the journal Nature Materials, Carlo Montemagno, professor and chair of the UCLA Department of Bioengineering, reports that his group has developed a chemical switch that gives them control over a biomolecular motor just 11 nanometers, or 11 billionths of a meter, in size ? hundreds of times smaller than the width of a human hair.

Montemagno first engineered nano-sized devices in 2000 when he altered a molecular motor protein by attaching tiny metal propellers to it. This motor protein, which exists naturally in all living cells, consists of six molecular structures forming the equivalent of a three-cycle motor, with a seventh molecule in the middle acting as the rotor. The motor draws its energy from the same fuel molecules that power living cells in every human body, a high-energy molecule called adenosine triphosphate, or ATP. Consumption of three ATP molecules is required to complete one rotation of the motor.

Gaining control over the motor’s operation brings scientists closer to the possibility of making machines that live inside the cell, according to Montemagno. “We’ll be able to enhance the capabilities of cells and ultimately enhance human performance,” he said.

In previous tests, the motor completed eight revolutions per second, but before now Montemagno had no way of turning the motor off. Instead it continued to run until it used up all its fuel or was destroyed. “It was like driving a car at full throttle until it runs out of gas,” Montemagno said.

Now researchers have modified the motors so that adding metal ions such as zinc to the motor can stop it, much like lodging a stick into the gears of a machine.

When Montemagno wants to restart the motor, he removes the metal from the motor, leaving it free to run once more. “This kind of control is critical to creating a useful device,” Montemagno said. “Now the motor can respond to its environment and carry out specific tasks.”

For example, medical sensors, fueled by the human body and powered by biomolecular motors, could be used to diagnose and treat diseases such as cancer. Once a cancerous tumor is found, a motor protein-powered device could deliver drugs directly to the diseased area. This enables drugs to be kept benign until they reach the tumor, limiting their activity to the diseased area.

Jacob Schmidt, UCLA assistant professor of bioengineering, said the addition of the metal did not measurably change the mechanical properties of the motor.

It also appears that the chemical activity of the motor continues even if the metal has stopped mechanical activity. “It’s like the clutch is disengaged in your car,” Schmidt said. “We’re still burning gas, but not going anywhere.”

This fusion of engineered devices and living systems will have tremendous impact on life sciences research in the near term, and may result in a number of applications, “but that’s still five to 10 years down the road,” Montemagno said.

The work was a collaboration with researchers at Duke University and was funded by NASA, the Defense Advanced Research Projects Agency and the National Science Foundation.

Montemagno’s team is now focusing on other issues, such as how to create large numbers of the motors and how to fuel them appropriately.