Ignoring 9,999 proteins and just studying one seems to just about work

In a couple of weeks I will be amongst Princeton‘s dreaming spires, on the other side of the Atlantic. I have been starting to write my talk over the last couple of days. A quick look at the programme suggests I will also be hearing about some work what are called nucleoli — these are structures in the nucleus of cells that make ribosomes; ribosomes are the nanoscale factories that make protein molecules. So they are basically the factories that make the factories that make proteins.

In a nutshell, Weber and Brangwynne present the hypothesis (pdf here) that you can model the nucleolus as a liquid droplet of a particular protein, coexisting with a solution of this protein in the rest of the nucleus. In this model the total volume of the nucleoli in the cell is just given by the amount of this protein that does not dissolve in the rest of the nucleus.

This is a simple idea from the basic chemistry of solubility. For example, consider sugar. It is very soluble in water*: 2 kg can dissolve in 1 litre (at 25 C), so if I add 5 kg to a litre of water then 2 kg dissolve, giving me 3 kg or about 2,000 cm³ of solid sugar** coexisting with a saturated solution of 2 kg of sugar in one litre of water. But if I add another litre of water then another 2 kg dissolves, and I only have about 1 kg or 670 cm³ of solid sugar coexisting with 2 litres of saturated sugar solution. So the bigger the volume of water, the smaller the volume of sugar left undissolved.

The idea here is that the mother C. elegans makes enough of this protein for the egg that develops into the embryo, to make nucleoli that are of the correct volume, taking into account the amount of this protein dissolved in the rest of the cell.

This model predicts that if you make the nucleus volume larger, more of this protein dissolves in the larger volume and so the volume of the nucleoli decreases. This is what Weber and Brangwynne observe, so the data support the model. Good work.

But there is a lot of scatter in the data, i.e., although there is a trend to smaller nuceoli volumes with increasing nucleus volumes, for a given nucleus volume, some cells have a lot bigger nucleoli than others. I did worry about this, but on reflection it is probably what you should expect. They study one protein, called FIB-1, but there are maybe ten thousand other proteins in the cell, which they neglect. The partitioning of FIB-1 between the  nucleoli and the rest of the cell must be affected by at least some of them.

In my sugar analogy, the solubility of sugar in water is only equal to 2 kg/litre if we only mix sugar and water. If you add fructose, glucose, maltose, etc as well, then the solubility of sugar in water will change. Given the 9,999 other proteins around, that Weber and Brangwyne neglect, it is actually pretty impressive that even a rather noisy correlation survives. And for practical reasons you can’t take account of 9,999 other proteins, neglecting them is kind of the only thing you can do. It may be that varying amounts of other proteins are causing the scatter but leave the correlation intact. It is nice work in any case.

* You may want to bear this mind before you buy a soft drink. Soft drink makers can get a lot of sugar in a can. One litre of water can dissolve an amount of sugar that the UN reckon you should not exceed in a month.

** The density of sugar is roughly 1.6 g/cm³ so 1 kg of sugar is about 670 cm³.

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