Lipids help regulate important cellular processes such as cell proliferation and immune response. Problems with lipid signalling have been linked with a number of diseases including cancer, diabetes, autoimmune diseases, and inflammatory conditions. “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,” explains Wonhwa Cho, a chemistry professor at the University of Illinois at Chicago. “While the exact mechanism is still unknown, our hypothesis is that lipid molecules serve sort of like a sliding switch.” Cho adds that it is “not just the presence of lipid, but the number of lipid molecules that are important for turning on and off biological activity.”
Up until now, however, there hasn’t been a method of quantitatively tracking lipids within living cells. To remedy that problem, Cho led a team of researchers at the university in the development of a biosensor that uses modified proteins to fluoresce and act as sensors for lipid levels.
As the press release explains:
While visualizing lipid molecules with fluorescent proteins isn’t new, Cho’s technique allows quantification by using a hybrid protein molecule that fluoresces only when it binds specific lipids. His lab worked with a lipid known as PIP2 — an important fat molecule 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 recognizes a particular lipid,” Cho said. He has been working on the technique for about a decade, overcoming technical obstacles only about three years ago.
Cho hopes now to create a tool kit of biosensors to quantify most, if not all lipids.
“We’d like to be able to measure multiple lipids, simultaneously,” he said. “It would give us a snapshot of all the processes being regulated by the different lipids inside a cell.”
Abstract in Nature Chemistry: In situ quantitative imaging of cellular lipids using molecular sensors