The biophysical properties of the cytoplasm rapidly change in response to different cellular stresses. Cells are highly crowded with mesoscale particles (10 nm to 1 mm in diameter) and this crowding regulates cellular functions by both hindering the motion of mesoscale particles and driving the assembly of mesoscale structures. Despite the importance of these processes, their underlying mechanisms are not well understood. Xie et al. now describe how various stresses change cytoplasm crowding and thus fluidization, and the ensuing consequences.

In the cytoplasm, the concentration of ribosomes (which have a diameter of 25 nm) is a major determinant of mesoscale particle diffusivity. In rapidly proliferating yeast cells, most ribosomes engage in protein translation and are organized into large polysomes; however, an almost universal response to stresses such as nutrient starvation is translation suppression, which results in polysome disassembly and the release of ribosomes and mRNA. Polysome profiling indicated that within minutes of stress induction, the fraction of ribosomes organized in polysomes was dramatically reduced. By contrast, combining stress with cycloheximide treatment, which prevents polysome disassembly, completely abolished the observed increase in stress-induced diffusivity. Thus, polysome disassembly is crucial for the transient increase in cellular fluidity following stress.