Smart polymers provide size-selective switches to turn proteins on, off

Researchers at the University of Washington have discovered a new method of regulating how proteins bind with specific molecules, a finding that gives scientists a size-selective �switch� to turn protein function on and off and moves a step closer to one of the �holy grails� of bioengineering.

The discovery, scheduled to appear in the journal Nature this week, has a number of possible applications in fields ranging from medical diagnostics to environmental sensing and computer science.

�This is what we call a platform technology,� said Patrick Stayton, associate professor of bioengineering. He and colleague Allan S. Hoffman, professor of bioengineering, lead the research group. �The basic idea is to be able to turn proteins on and turn them off, which has been one of the holy grails of bioengineering. It�s very exciting and can apply in a lot of different areas.� The latest finding builds on earlier work by the group exploring 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, such as temperature, acidity and light.

In the earlier research, Stayton, Hoffman and their colleagues attached tiny smart polymer chains next to active sites on a protein. �The idea was that as the polymer changed its properties, it would collapse into a compact globule to block the site,� Stayton said.

�When it extended, it would allow a molecule that recognizes the site to attach. And if you collapsed the polymer and a molecule were already attached, the collapsing polymer could kick it off the site.�

The key, he said, was that the process was reversible, allowing scientists to control proteins in �grabbing� specific molecules, then letting them go on command. The problem was that, with the polymer attached so closely to the site, the process worked only for small molecules. The polymer, even when collapsed, wouldn�t allow larger molecules to bind.

The latest work offers a rather surprising solution, according to Stayton, one that runs directly opposite of the earlier process. Researchers found that if they moved the polymer chain farther from an attachment site, the extended chain would shield the site, blocking a larger molecule from attaching. However, when coiled, the chain was far enough out of the way so the big molecule could bind to the site.

The group also discovered a close correlation between the size of the polymer chains and the size of the molecules affected. �So we can be very specific about what we want to target,� Stayton said. He added that the property change of the smart polymer is striking � a small environmental change triggers an abrupt shift. �It acts like a switch.�

Those factors could allow scientists, for example, to specifically target what they want to cull from a solution such as a blood sample. The proteins could be engineered to pull a specific molecule from the sample and hold it until the rest of the blood had been washed away. The proteins could then be prompted to release the desired material.

�This switch idea in combination with the shield concept allows you to discriminate on the basis of size,� Stayton said. �It adds a greater level of responsiveness to things like diagnostics, which usually involve steps of capture and release.� Computing is another area in which the technology could apply. Computers operate on a binary system � they rely on having an �on� and an �off� state.

�Typically, that�s done with non-biological components now,� Stayton said. �This indicates another, very nice way to do it.� The diminutive size of the proteins and molecules involved could open avenues into advanced concepts like �lab on a chip� � the ability to fit a full range of laboratory functions on a single computer chip. They may also serve as useful components for chip technologies involving such disciplines as genomics.

In the published research, the scientists used changes in temperature or acidity to trigger the smart polymers. But in more recent studies they�ve been able to activate the polymers using a third factor � light.

�Light is the really interesting one,� Stayton said. �The response is to two different wavelengths of light. You can turn them on with visible light, then turn them off with a separate range of ultraviolet light. It really is a true switch.�

For more information, contact Stayton at (206) 685-8148, 616-2367 or [email protected] or Hoffman at (206) 543-9423 or [email protected]