From the WashU Newsroom…
Inside each and every living cell, there are miniscule structures called membraneless organelles. These tiny powerhouses use chemistry to cue the inner workings of a cell — movement, division and even self-destruction.
A collaboration between engineers at Princeton University and Washington University in St. Louis has developed a new way to observe the inner workings and material structure of these vitally important organelles. The research, published today in Nature Chemistry, could lead to a host of new scientific applications, as well as a better understanding of diseases such as cancer, Huntington’s and amyotrophic lateral sclerosis, or ALS.
“They’re like little drops of water: They flow, they have all the properties of a liquid, similar to raindrops,” said Rohit Pappu, the Edwin H. Murty Professor of Engineering at Washington University’s School of Engineering & Applied Science. “However, these droplets are comprised of protein that come together with RNA (ribonucleic) molecules.”
In the past, peering into organelles has proven difficult due to their tiny size. Clifford Brangwynne, associate professor in chemical and biological engineering at Princeton’s School of Engineering and Applied Science, and his collaborators developed a new technique — called ultrafast scanning fluorescence correlation spectroscopy, or usFCS — to get an up-close assessment of the concentrations within and probe the porosity of facsimiles of membraneless organelles. The approach uses sound waves to control a microscope’s ability to move and then obtain calibration-free measurements of concentrations inside membraneless organelles.
In their research, Brangwynne and his team, including postdoctoral researchers Ming-Tzo Wei and Shana Elbaum-Garfinkle, used cells taken from a roundworm. With usFCS, they were able to measure protein concentrations inside organelles formed by the specific protein LAF-1. This protein is responsible for producing p-granules, which are protein assemblies responsible for polarizing a cell prior to division. Once the Princeton researchers were able to clearly peek into the organelles and view the LAF-1, what they found surprised them.
“We found that instead of being densely packed droplets, these are very low density, permeable structures,” Brangwynne said. “It was not the expected result.”
That’s when Washington University’s Pappu and his graduate research assistant Alex Holehouse tried to make sense of the surprising findings from the Princeton group. Pappu’s lab specializes in polymer physics and modeling of membraneless organelles.
“We were able to basically swim inside the organelles to determine how much room is actually available. While we expected to see a crowded swimming pool, we found one with plenty of room, and water. We’re starting to realize that these droplets are not all going to be the same,” Pappu said.
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