Lipid Biosensor Could Eventually Be Used to Treat DiseasesLipid Biosensor Could Eventually Be Used to Treat Diseases

Researchers from the University of Illinois at Chicago (UIC) have developed a biosensor that measures membrane lipid levels, paving the way for new techniques of treating disease. Created by Wonhwa Cho, UIC professor of chemistry, and his coworkers, the technology is based on a method of modifying proteins to fluoresce so that they can act as sensors to measure lipid levels.

"Lipid molecules on cell membranes can act as switches that turn on or off protein-protein interactions affecting all cellular processes, including those associated with disease," Cho explains. "While the exact mechanism is still unknown, our hypothesis is that lipid molecules serve sort of like a sliding switch."

Once lipid concentrations reach a certain threshold, they trigger a range of reactions, including disease-fighting immune responses, Cho says. Quantifying lipid-membrane concentrations in a living cell and studying its location in real time can provide a tool for understanding and developing new ways to combat a range of illnesses, including inflammation, cancer, diabetes, and metabolic diseases.

"It's not just the presence of lipid, but the number of lipid molecules that are important for turning on and off biological activity," Cho adds. While visualizing lipid molecules with fluorescent proteins isn't new, the UIC researchers' technique enables them to quantify the lipids by using a hybrid protein molecule that fluoresces only when it binds specific lipids. Cho's lab has worked with a lipid known as PIP2--an important fat molecule that is involved in many cellular processes. Cho's sensor binds to PIP2 and gives a clear signal that can be quantified through a fluorescent microscope. The result is the first successful quantification of membrane lipids in a living cell in real time.

"We had to engineer the protein in such a way to make it very stable, behave well, and specifically recognize a particular lipid," Cho remarks. Although he has been working on this technique for about a decade, it was only within the last three years that he and his team overcame the technical obstacles that were impeding success. Eventually, the scientists hope to create a toolkit of biosensors that can quantify most, if not all, lipids.

"We'd like to be able to measure multiple lipids simultaneously," Cho says. "It would give us a snapshot of all the processes being regulated by the different lipids inside a cell."