Like oil in water

How does the nucleolus, a compartment in cells that is not surrounded by a membrane, interact with its surroundings?
Digest
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Nuclei of cells (green) with the nucleoli marked in red. Image Credit: Christina M. Caragine and Alexandra Zidovska (CC BY 4.0)

The inside of a cell is very organized. Just as bodies contain internal organs, cells contain many different compartments, called ‘organelles’, each with its own specific role. Most organelles are surrounded by a membrane that keeps their contents separate from the cytoplasm, the water-based liquid inside the rest of the cell.

Some organelles, however, are not bounded by a membrane. Instead, they act like tiny drops of oil in water, retaining their structure because they have different physical properties from the fluid around them, a phenomenon called liquid-liquid phase separation.

One such organelle is the nucleolus, which sits inside the cell’s nucleus (a membrane-bound organelle containing all the genetic material of the cell in the form of DNA). The nucleolus’s job is to produce ribosomes, the cellular machines that, once transported out of the nucleus, will make proteins.

Human cells start with 10 small nucleoli in the nucleus, which fuse together until only one or two larger ones remain. Previous research showed that nucleoli form and persist thanks to liquid-liquid phase separation, and they behave like liquid droplets. Despite this, exactly how nucleoli interact with each other and with the fluid environment in the rest of the nucleus remained unknown. Caragine et al. set out to measure the behavior and interactions of nucleoli in living human cells.

Microscopy experiments using human cells grown in the laboratory allowed the positions, size and shape of nucleoli to be tracked over time. This also yielded detailed information about the smoothness of their surface. Mathematical analysis revealed that pairs of nucleoli normally moved independently of each other, unless they were about to fuse, when they invariably slowed down and coordinated their movements. In addition, altering the state of DNA in the surrounding nucleus also affected the nucleoli. For example, when DNA was less densely packed, nucleoli shrank and their surfaces became smoother.

These results build on our knowledge of how cells are organized by showing, for the first time, that the environment within the nucleus directly shapes the behavior of nucleoli. In the future, a better understanding of how cells maintain healthy nucleoli may help develop new treatments for human diseases such as cancer, which are characterized by problems with this organelle.