In vitro cell cycle oscillations exhibit a robust and hysteretic response to changes in cytoplasmic density

The cytoplasm, where most cellular reactions occur, has a variable density. We currently lack an understanding of how density variations affect cellular functions because of the challenge of controlling it experimentally. Here, we systematically modulate the density of an in vitro cytoplasm using microfluidics and analyze how the cell cycle behaves in turn. We found that mitotic cycles maintain their function across 0.2× to 1.2× of the natural density. Higher densities arrest cell cycles, and dilution recovers oscillations. However, the density at which cycles reappear is lower than the natural density. This behavior suggests a history-dependent mechanism called hysteresis, common in physics, chemistry, and engineering. Our approach paves the way for studying the responses of other processes to density changes.