A groundbreaking single-protein analysis technique developed by researchers at Weill Cornell Medicine and Ruhr University Bochum in Germany is providing an unprecedented look at scramblases, proteins that play critical roles in biology by rearranging lipids within cell membranes. The study, published June 15 in Nature Structural & Molecular Biology, introduces a fluorescence imaging-based method that measures the activity rates of individual scramblase proteins for the first time.
This new platform overcomes limitations of traditional bulk analysis, which averages the activity of many proteins and misses important variations. Using this technique, the team studied VDAC1, a mitochondrial channel protein also known to act as a scramblase.
They discovered that VDAC1 dimers exhibit a wide range of scrambling rates, from fewer than 100 to over 1,000 lipids per second, confirming predictions from computer simulations. The method also revealed that opsin, a light-detecting receptor in the eye, scrambles lipids at rates exceeding 10,000 per second.
The researchers believe this versatile tool can be used to study how scramblase function is affected by changes in membrane lipid composition or by drug molecules, and they plan to apply it to other lipid-moving proteins like flippases and floppases. The work was supported by the National Institute of General Medical Sciences, Canadian Institutes of Health Research, and Deutsche Forschungsgemeinschaft.