Smart polymers provide light-activated switch to turn enzymes on and off

Researchers at the University of Washington have applied research in how proteins bind with different molecules to create a molecular switch that enables them to turn an enzyme on and off. The innovation holds promise for a wide range of laboratory processes, including highly targeted drug therapies.

The study, published this week in the Proceedings of the National Academy of Science, describes a reversible switch for the enzyme endoglucanase in which light is the trigger for turning the switch on and off.

An enzyme is a protein that acts as a catalyst in initiating or speeding up a chemical reaction in the body. Endoglucanase facilitates the breakdown of cellulose.

The latest research builds on earlier work by the group in the use of so-called “smart polymers” to control access to binding sites on proteins. The polymers are described as “smart” because they sense their environment and alter their properties according to changes in external conditions. The conditions in the earlier work that prompted the polymers to react were temperature and acidity. The latest findings are even more exciting, according to Patrick Stayton, UW professor of bioengineering, because the trigger is light.

“Light is the real interesting one,” said Stayton, who, with colleague Allan S. Hoffman, professor of bioengineering, leads the group, which also includes researchers from Genecor International, a California biotech firm. “It’s easily reversible ? it really is a true switch.”

To build the switch, the researchers attach tiny smart polymer chains next to the active sites, or the spots where the enzyme binds with target molecules to do their work. Depending on conditions, the polymer threads either extend or contract. One state blocks the site, while the other leaves it open ? which state accomplishes which function depends on the size of the target molecule.

In the case of endoglucanase, a contracted polymer thread blocks the site and an expanded one moves away from the site, leaving it open. Researchers synthesized two light-sensitive polymers, called DMAA and DMAAm. When exposed to visible light, DMAA becomes hydrophilic ? it attracts water molecules and expands. When the visible light is replaced by ultraviolet light, DMMA becomes hydrophobic, expelling the water molecules and contracting into a coil. DMMAm works in reverse: under UV light it expands, and under visible light it contracts.

So the switch works by enabling endoglucanase to bind or unbind with cellulose, depending on the type of light applied.

The technique should be useful over a broad range of applications.

The diminutive size of the enzymes and molecules involved could open avenues into advanced concepts like microfluidics and “lab on a chip” ? the ability to fit a full range of laboratory functions on a single computer chip. The technique could also be valuable in drug therapies that involve an enzyme that needs to remain inactive until it reaches its target.

“Once in place, they could be activated using optical fiber technology,” Stayton said.