Giant germs, making a mockery of physics

One of the reasons I went into Physics is the absoluteness of its claims: every proton has an electric charge; every bit of mass generates a gravitational field; and so on. One of the dizzying yet fascinating things about biology is, often, its lack of universality — nearly every statement one can make has some exception. For example: bacteria are small.

Biophysically speaking, the smallness of bacteria makes sense. Bacteria lack motor proteins (as far as anyone knows), and so rely on diffusion for the transport of molecules. Some DNA-binding protein, for example, released from the membrane in response to some stimulus, will simply randomly stumble about in the cell until it happens to reach its DNA target. A typical protein diffusion coefficient is ~100 um^2/s, and a typical bacterial size is ~ 1 um, so we can expect the travel time of a wandering protein to span the cell be around 10 ms — fast enough to make cellular decision-making possible. Phrased a different way: if a cell needs information to be relayed within 10 ms and relies only on diffusion, it can’t be more than about a micron in size. And so that’s what bacteria are. The famous E. coli, for example, is a roughly 1×3 um rod.

The bacterium Epulopiscium, however, is several hundred microns long. As described in an excellent short essay by Mark Buchanan in this month’s Nature Physics, the creature “can be as long as 600 μm and one-fourth as wide.” The question I posed to my class:

How does it do it? Use your imagination, and think of at least one way around the limitation described above.

You, dear reader, should also think about this; the bacterium’s solution is described below, along with responses from the students.

While you’re thinking, you can stare at my illustration of Epulopiscium together with E. coli, roughly to scale, which was a bit challenging to arrange…

Pause…

There are lots of solutions one can imagine. Some that the students came up with (after the initial terror of being asked to imagine things subsided, and after quite a bit of discussion with their neighbors):

• The bacterium somehow compacts itself to be smaller.
• Rather than free fluid, the bacterial interior has small “channels” or tubes through which things move, restricting the space to diffuse through.
• It’s really hot inside the bacterium (and so diffusion is faster).
• There are multiple regions inside the bacterium to which proteins can diffuse; there are not single targets.
• Perhaps the bacterium has things like motor proteins in it. (We’ve noted previously that eukaryotic cells are larger, typically 10 microns or more in length, but they don’t rely on diffusion for everything and instead actively transport cargo using motor proteins.)
• Proteins might somehow signal to other proteins to follow their path, perhaps by binding to them, so they all wouldn’t have to move randomly.
• I added one: Maybe the bacterium just lives very slowly. It takes a protein a minute to reach its target — so what? We’ll just lethargically wait until this happens, and have a very slow metabolism and lifestyle.

What does the bacterium actually do?… One of the responses was very close to the mark: the guess that there are multiple targets to diffuse to. Epulopiscium, it turns out, has about 10,000 copies of its genome — 10,000 copies of its DNA — and their associated machinery! In other words, it cheats: rather than having 1 copy of its genome like an honest bacterium, it’s like 10,000 bacteria masquerading as one. With so many copies, each local neighborhood has a full complement of components, and can be rapidly spanned by diffusion. (See the Nature Physics article and its references for some glimpses of other issues related to this bacterium.)

I’m disappointed, perhaps because I often feel that life moves too fast, that the bacterium didn’t adopt my suggestion of adopting a very slow lifestyle. I would also have liked to imagine a little bacterial furnace, generating very high temperatures. Epulopiscium lives in the stomachs of surgeon fish, though, and perhaps the fish would object. It’s a neat coincidence that my lab devotes much of its effort to visualizing bacteria inside the fish digestive tract (zebrafish, not surgeonfish — at least not yet). We’ll keep an eye out for similarly strange biophysical adaptations.