Researchers at Weill Cornell Medicine and a German university have developed a new technique that allows scientists to measure the activity of individual proteins involved in critical cellular functions, a breakthrough that could advance research into diseases ranging from liver disorders to cancer.
The new method, described in the journal Nature Structural & Molecular Biology, enables researchers to study single scramblase proteins, which help rearrange fats known as lipids within cell membranes. Scientists say the technique offers a level of detail that was previously impossible to achieve.
Scramblases play important roles throughout the body, including helping build cell membranes, supporting muscle development, regulating cell survival and moving molecules within cells. Because these proteins are involved in so many biological processes, researchers believe they could eventually become targets for new drug therapies.
Until now, scientists typically studied large groups of scramblase proteins at once, averaging their behavior rather than measuring individual activity. The new fluorescence imaging technique allows researchers to isolate single proteins and determine how quickly they move lipids across cell membranes.
“I’m excited about this new platform as it is versatile and provides unprecedented information on exactly how fast a single scramblase works,” said Dr. Anant Menon, a professor of biochemistry and biophysics at Weill Cornell Medicine and co-senior author of the study.
Using the new approach, researchers discovered significant differences in activity among individual proteins. In one experiment involving a protein known as VDAC1, scrambling rates ranged from fewer than 100 lipids per second to more than 1,000. Another protein called opsin, which is involved in vision, moved lipids at rates exceeding 10,000 per second.
Researchers said the findings could help explain how these proteins function and why they sometimes become dysfunctional. The team plans to use the technology to study how medications and changes in cell membrane composition affect protein behavior.
Looking ahead, scientists believe the platform may help uncover new strategies for treating a variety of diseases and could eventually be adapted to study other classes of lipid-moving proteins that play key roles in human health.
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