Biomolecular condensates are shifting blobs in our cells that organize cellular matter. They are distinct molecular communities made of DNA, RNA and proteins that “condense” molecules to key locations, yet they frequently defy description. Partly this is because they are so small, they cannot be measured using traditional microscopes.
“These blobs were once described as being ‘liquid-like’ because some of them were observed to kiss, fuse, drip and flow like raindrops on windshields,” said Rohit Pappu, PhD, the Gene K. Beare Distinguished Professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St. Louis.
However, while the blobs may look like raindrops, computations have suggested otherwise. The molecular organization within condensates is more like that of a network that rearranges on different time scales, giving condensates more of a shifting, Silly Putty-like character.
Working with the lab of Matthew Lew, PhD, an associate professor of electrical and systems engineering at McKelvey Engineering, Pappu and colleagues, all members of the WashU Center for Biomolecular Condensates, tested computational predictions by peering into condensates using novel super-resolution microscopy methods.
In research published March 14 in Nature Physics, the Pappu and Lew labs show how to employ fluorogens — environmentally sensitive dyes that only light up in certain chemical environments — to peer into condensates at high resolutions that scientists have previously been unable to achieve. They used these fluorogens one at a time, aided by unique imaging technologies developed in the Lew lab.
These advances in imaging are central to understanding how condensates function and how they go awry in the context of cancers and neurodegenerative diseases, which are associated with functionally aberrant condensates.