Understudied Protein Blobs Have Global Effects on Cell Biochemistry
Published:11 Nov.2024    Source:Duke University
Most biological chemistry research has historically focused on the obvious cogs of machinery that keep life moving. Folding proteins, genetic activity and electrical signaling pathways are the easiest targets for finding irregularities that lead to disease. Recent research, however, has pointed to a different type of cellular structure that may play an equally important role. These structures called biological condensates. Previous studies have shown that these blobs can separate or trap together certain proteins and molecules, either hindering or promoting their activity. Previous studies have shown that these blobs can separate or trap together certain proteins and molecules, either hindering or promoting their activity.
 
Now, in a new study published September 10 in the journal Cell, researchers from Duke University and the Washington University in St. Louis have shown that the formation of biological condensates affects cellular activity far beyond their immediate vicinity. The results show that they may be a previously missing mechanism by which cells modulate their internal electrochemistry. And those internal controls, in turn, affect the cellular membrane, which allows these unassuming blobs to affect global traits and outcomes such as resistance to antibiotics. "Our research shows that condensates influence cells well beyond direct physical contact, almost like they have a wireless connection to how cells interact with the environment," said Lingchong You, the James L. Meriam Distinguished Professor of Biomedical Engineering at Duke. Condensates act sort of like a sponge, soaking up various proteins, enzymes, ions and other biomolecules when they form, while excluding others. This electrostatic activity provides a handle for the formation of biological condensates to affect the electrical potential of the cellular membrane and the electrochemical environment within the cell.
 
This paper shows there is no escape from these effects. As long as these tiny blobs form, many things are influenced, even gene regulation in a global scale. When I saw that, it was quite shocking to me. To prove this point, the researchers worked to show that this phenomenon can affect how well bacteria survive interactions with certain antibiotics. The results showed that condensate formation caused some cellular membranes to become more negatively charged, which directly affected whether or not the cells reacted to the antibiotics, since they are also charged particles. "Our work uncovers a role of condensates in regulating global cellular physiology," You said. "While we don't yet have a concrete mechanistic understanding of how cells are deploying this activity to regulate their functionality, it's a major discovery that it's happening at all."