New NMR approach for studying droplet-shaped cell content
Researchers in Utrecht have found a new way to observe membrane-free compartments at an unprecedented level of resolution. The existence of these so-called biomolecular condensates in the cell contradicts all school textbooks on the subject. This is the first time they have been observed in test tubes with high accuracy. The researchers and their German colleagues will publish their results in Nature Communications on October 4, 2019.
High school students are still learning that the cells contain organelles surrounded by a membrane, but their biology textbooks are now obsolete. In recent years, scientists have known that in addition to membrane-covered organelles, such as mitochondria and Golgi complex, there are also membrane-free compartments in the cell called biomolecular condensates.
These "droplets" consist of proteins and RNA, and are distributed throughout the cell. Condensates sometimes form islets: The concentration of some proteins suddenly increases, creating clusters of molecules. This occurs everywhere in the cell, in the cytoplasm, but also in the nucleus," explains the latest author Marc Baldus from Utrecht University. "It's completely different from what's in the manuals. Not everything has a fixed position, as we have always thought; even DNA can form these droplets."
Droplets
Scientists have known these membraneless compartments for some years, but the resolution of a normal microscope, tomography and MRI have not been sufficient to visualize the dynamic nature of these droplets at the atomic level. The University of Utrecht has advanced magnetic resonance (NMR) equipment for the observation of complex systems. In this study, the researchers worked with the group led by Remco Sprangers at the University of Regensburg to develop a new NMR approach to studying proteins that form droplets: a combination of "solid state" and "solution" NMR.
"A large part of proteins do not have a fixed structure; they move from one form to another. The unfolded parts of the protein can move quickly and are available to interact with other proteins. We can now follow these high-resolution processes; where the protein binds, to what other protein it binds, and we can eventually see how fast it also occurs," says Baldus.
Diseases
Biomolecular condensates often contain proteins that play a role in diseases such as cancer, Alzheimer's disease and ALS. "That's why the pharmaceutical industry is also interested: a better knowledge of their structure could make it possible to administer drugs more accurately," explains Baldus. "But this is the second step. For the first time, we have proven that we can study these droplets at the highest resolution, and now we will start to identify all the details in these systems."
