Protein phase separation

Remember learning about the parts of a cell in school? In a eukaryotic cell there’s the nucleus, which has a membrane that separates itself from the rest of the cell, and I was okay with that. Then I learned about the nucleolus – a membrane-less part of the nucleus, and I wasn’t a big fan. If it doesn’t have a membrane, how does it stay separated from the rest of the nucleus? No one taught me about phase separation.

Inside of cells, dense droplets of protein (along with DNA and RNA) form and redissolve depending on the conditions of the cell, where these droplets are responsible for useful functions in our bodies. In the case of the nucleolus, the density of pieces presumably helps it with the complicated task of ribosome synthesis. However, the nucleolus must be dynamic during the cell life cycle.

In general, if something goes wrong in a phase separating system (ex: separation stops being reversible) serious conditions like cataract formation or Alzheimers can occur. Therefore, understanding how and why proteins phase separate can lead us towards understanding both how our body works and how to prevent/cure some diseases.

I had a visitor from Lewis Kay‘s group in Toronto come down to do some experiments. He brought with him some samples of protein that are known to phase separate in cells. At high temperatures, the proteins are dispersed but form droplets when cooled. The image below is of droplets forming as the sample temperature is lowered. It can also be found on the Georgetown University Physics’s department twitter account. You can see that the droplets are liquid-like because some coalesce between frames. Enjoy.