Thread by @JoelLemiere

Very pleased to share that my latest story from my time in @fredchanglab @UCSF is now accepted at @eLife. Control of nuclear size by osmotic forces in Schizosaccharomyces pombe doi.org/10.7554/eLife.…

Before I try my best to summarize it I want to thank all co-authors @fredchanglab, @ThomasGFai, @LiamHoltLab and @WallaceUcsf for organising the #QCBNet #NSFfunded hackathon.

We developed a quantitative model for nuclear size control based upon colloid osmotic pressure and tested key predictions in fission yeast. We called it: Model of the nucleus and the cell as “a vesicle within a vesicle”.

The first thing we found is that the nucleus behaves like an ideal osmometer! This means that its volume is directly responsive to its osmotic environment. It also implies that tension of the nuclear envelope is negligible.

We then show that the N/C ratio does not depend on the tension exerted on the cell (cell wall / cortex) and is also maintained upon osmotic shocks. Both behaviors being predicted by our model in the case of negligible NE tension.

We determined how cytGEMs movement relates to macromolecular crowding thanks to protoplasts. Indeed, cytGEMs diffusion could be fit with a model that predicts a tracer particle’s self-diffusive behavior in a wide range of polymer concentrations.

We used nucGEMs and CytGEMs to probe the nucleoplasm and cytoplasm macromolecular crowding. We found that it is affected similarly under osmotic shocks. It means that the macromolecular concentration of both compartments changes proportionally when osmotically challenged.

We used LMB to inhibit nuclear export. LMB causes an increase in the number of macromolecules in the nucleus, but it also causes a progressive decrease in the number of macromolecules in the cytoplasm. The nucleus responds to these shifts by equilibrating to a larger size.

What happens if you dilute similarly the cytoplasm and nucleoplasm then? Well, proportionate dilution of macromolecular components in both compartments did not alter the N/C ratio, as one would expect if nucleus behaves like an ideal osmometer !

Finally we propose a simple model for nuclear size control. We assumed that volume growth is driven by the rate of biosynthesis of cellular components that scales with the cytoplasm volume. All parameters in our model could be experimentally measured – no free parameters hidden!

The model predicts that the rate at which cells born with an aberrant N/C ratio correct it is the opposite of cell growth. We tested this on Δpom1 cells and by reducing cell’s growth rate – Our experimental data were an excellent fit in both cases.

Conclusion: it shows that the continued growth of the cell and nucleus is sufficient to explain the correction of the N/C ratio without having to invoke an active mechanism.