Coordination of nuclear and cellular volumes in fission yeast

The size of the nucleus typically scales with cell size, maintaining a constant nuclear-to-cell volume ratio (N/C ratio) across many cell types. Although the mechanisms that establish the N/C ratio remain unknown, it has been known for decades that alterations in this ratio are a hallmark of diseases and are used, for example, to determine cancer stage.

We developed a quantitative model for nuclear size control, based upon a balance of colloid osmotic pressures between the nucleoplasm and cytoplasm. This model posits that the N/C ratio is determined by an equilibrium between nuclear envelope membrane tension and osmotic forces generated by the numbers of macromolecules in both compartments. Osmotic shift experiments in the fission yeast S. pombe show that the nucleus behaves as an ideal osmometer whose volume is primarily dictated by osmotic forces, with no detectable contribution of membrane tension. Thus, we predict that the key determinants of nuclear size in fission yeast are simply the numbers of macromolecules.

Here, to test this ideal osmometer model for nuclear size, we massively loaded an osmotic agent into either the nucleus or cytoplasm of fission yeast. When the nucleus was filled with additional macromolecules, we observed nuclei that were up to four times larger, increasing the N/C ratio from a standard value of 8% to as high as 30%. Conversely, adding macromolecules to the cytoplasm decreased nuclear volume and the N/C ratio by half. In both cases, the resulting N/C ratio aligned with our model’s prediction for pure osmotic control of nuclear volume. Thus, we have developed a system in which we can predictively alter the nuclear-to-cell volume ratio by modifying the fraction of osmotically active particles transported into the nucleus.