Why do biomolecular condensates ripen so slowly?

It has recently become clear that the interiors of cells are organized in both space and time by non-membrane bound compartments, many of which form via liquid-liquid phase separation. These phase-separated condensates play key roles in processes ranging from transcription to translation, signaling, and more. While the thermodynamic ground state of two immiscible liquids is a single droplet of one liquid immersed in the other, in cells natural and synthetic condensates typically appear as multiple, dispersed droplets. In this talk, I will focus on two potential mechanisms for a slowdown of droplet coarsening: (1) Droplets’ coalescence and ripening can be mechanically suppressed in the cell nucleus due to the presence of the viscoelastic chromosomal DNA. (2) For molecules that are capable of self-collapsing into a “non-sticking” conformation, ripening can be further slowed by a bouncing effect, i.e., incident molecules can contact the interface without entering the dense droplet. More generally, I will discuss cellular strategies for regulating the number, size, and placement of condensates, with implications for both natural and synthetic systems.