Biologists arguing over liquids

Balsamoil Protean

Chemical engineers, chemists, physicists and food scientists have been studying coexisting liquids like the (black) balsamic vinegar and (yellow) olive oil above, for over a hundred years. Cell biologists have been busy with other things over this time. But over the last few years at least some cell biologists seem to not only be studying coexisting liquids but arguing over them.

Last year McSwiggen et al. published a paper looking at the behaviour of a protein complex that makes RNA from DNA inside the nuclei of cells. So far so normal, publishing papers on making one biomolecule, RNA, from another, DNA, is kind of what cell biologists do.

And they go on study what they call Replication Compartments or RCs. They show a pair of RCs coming together and coalescing, just a pair of balsamic droplets would do if they came together and touched when they are both inside the same puddle of olive oil.

So far so good. They have shown that their RCs behave just as the definition of a liquid tells us they should. A liquid is just anything that flows, and is not a gas — gases are much lighter than liquids. Their RCs are obviously not gases and they flow. Therefore they and the surrounding nucleus are either coexisting liquids or something entirely analogous*.

But they go on to say

“If RCs were a bona fide separate phase, one would expect differences in molecular crowding or intermolecular interactions to predominantly affect free diffusion, resulting in substantially different diffusion coefficients.”

Now they are arguing that RCs are not one liquid inside another, based on diffusion of a protein complex. But this is not how liquids are defined, you don’t have to know anything about how this or that molecule diffuses, to say it is a liquid. Wikipedia’s definition of what a liquid is does not mention diffusion or molecules. And so if you have two liquids, then in principle this or that molecule can diffuse how it likes in both of them.

I think McSwiggen et al.‘s point is basically that the complex diffuses in a very similar way inside and outside the RCs, and this argues against them being coexisting liquid. But there is no law forbidding this behaviour in a pair of coexisting liquids. For example different polymers mixed into the same solvent often separate out into two coexisting liquids, and often smaller molecules will behave in very similar ways in the two liquids.

Anyway, I have emailed the editor of the biology journal, eLife — which I think is a great journal — offering to a write a short what-are-liquids article, written for biologists. I suspect they will not take me up on this offer, but I could be wrong.

* Liquids are thermodynamic phases, i.e., strictly defined at thermodynamic equilibrium. Cells are not at thermodynamic equilibrium, so the RCs cannot just be simple liquids as they perturbed by the cell’s processes. But I don’t think McSwiggen and coworkers discuss this point.

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