The contents of eukaryotic cells are organized into various compartments containing membraneless organelles, formed by a process known as liquid-liquid phase separation. Researchers have experimented with creating artificial versions of these compartments to control various aspects of cell biology. For example, they block certain cellular responses or create new sites for protein translation. Now, the team, led by Matthew Goode of the University of Pennsylvania Perelman School of Medicine, has combined several recent advances in the technology to create membraneless organelles that reversibly store and release specific intracellular cargoes, allowing research allows researchers to control cell behavior more finely than before. can.To make the organelles, Good's team used yeast (and subsequently manipulated human cells). Then, to tag specific peptides as cargo for these artificial organelles, the researchers edited the cell's DNA to create versions of the peptides with tags. That is, another protein that interacts with the proteins that make up the condensate. Using fluorescent labeling and microscopy to observe the assembly in vivo, the team found that up to 90% of the labeled cargo protein was sequestered in droplets. The researchers then used this technique to control cell behavior. For example, labeling of her Cdc5, a protein required for cell division to be taken up by organelles, stops cells from proliferating. The team also showed how other cargo proteins could be used to reverse the process. By gently heating the cells to break the weak interactions between the condensed proteins and the tags, the cargo was released and cell behavior resumed. The researchers also engineered the cells to produce a light-sensitive protein between the cargo and its tag. "They show that you can actually influence cell signaling in this way," says Edward Lemke, a biophysical chemist at the Johannes Gutenberg University Mainz in Germany and his IMB Mainz. increase. "By concentrating [specific elements] in corners or releasing them from [cell's] corners, we can alter cell output and complex cell functions. . I think it's really cool just to show that it's possible. He adds that it will be interesting to see techniques applied to control the fate of multiple cells using the simultaneous presence of multiple types of organelles and cargoes. We recently did something similar and created different synthetic organelles. Each organelle served as a site for protein translation in addition to the cytoplasm, producing multiple versions of the same protein within a single cell.Goode says this type of real-time sequestration of intracellular material of choice by researchers could have a variety of applications. “This platform can be used in a kind of isolator mode, as in this article, in order to trap specific molecules, but it can also be used in bioreactor mode . As a means of accelerating.The researchers also want to see if they can use approaches to continuously release specific biochemical factors. It is the isolation and release of individual factors during the programming process.”

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