By Leah Shaffer
Much of cell behavior is governed by the actions of biomolecular condensates: building block molecules that glom together and scatter apart as needed. Biomolecular condensates constantly shift their phase, sometimes becoming solid, sometimes like little droplets of oil in vinegar, and other phases in between. Understanding the electrochemical properties of such slippery molecules has been a recent focus for researchers at Washington University in St. Louis.
In research published in Nature Chemistry , Yifan Dai, assistant professor of biomedical engineering at the McKelvey School of Engineering, shares the rules involving the intracellular electrochemical properties that affect movement and chemical activities inside the cell and how that might impact cell processes as a condensate ages. The research can inform development of treatments for diseases like ALS or cancer.
Extracellular flow, or the movement of ions between cell membrane channels, is well studied but little was known about those same electrochemical fields at play inside the cell.
"In the past century, people have learned a lot regarding electrochemical effects caused by extracellular environmental perturbances. However, in the intracellular world, we do not know much yet," said Dai.
This work is one of the very first steps to writing those rules, Dai and collaborators from Stanford University, including Professors Guosong Hong and Richard N. Zare, show condensation and the non-equilibrium process after condensation is itself a way to regulate the electrochemical dynamics of the environments.
Imagine a giant conference hall with lots of little groups of people looking at posters, constantly shifting in and out to different exhibits. Some of those people might want others to follow them to another exhibit or call attention to a different subject and bring others with them.
This is how condensates work, going where they stick, affecting the movements of other condensates with their electrical potentials, and changes to the pH of the surrounding environment. And, playing with the surface of those condensates can also affect the electrical potentials, as Dai and colleagues found.
They determined that electrochemical potential is also regulated by "aging-associated intermolecular interactions and interfacial effects."
Think about that conference hall of people, over the course of a full day, those interactions are less optimal as the individuals get tired and experience stress.
"The surface of the condensate is going to change during the aging process," Dai said.
Back in the molecular realm, these "aging associated" interactions can lead to dysfunction and disease like ALS and Alzheimer's so understanding how to potentially interrupt that could yield medical treatments.
They were able to adjust electrical potentials by modifying the surface of a condensate. By measuring the alignment of the molecule, they could also determine its surface potential for ion flow, and most importantly, find ways to manipulate those surface signals to push healthy biological reactions.
"Hopefully, this work can shed light on the concept that condensate is not just about biomolecules."
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Yu W, Guo X, Xia Y, Ma Y, Tong Z, Yang L, Song X, Zare RN Hong G, Dai Y. Aging-dependent evolving electrochemical potentials of biomolecular condensates regulate their physicochemical activities. Nature Chemistry. online March 12, 2025.
DOI: https://www.nature.com/articles/s41557-025-01762-7
Part of this work was supported by the Air Force Office of Scientific Research (FA9550-21-1-0170 to R.N.Z.).
