There is an interesting discussion over at lablit.com about the use of metaphor, or rather analogy in science.
Just under two years ago I gave a talk to my group about some work I’d been involved with in Cambridge (where I had just left). The things that people remembered from the talk are me ping ing a marble across the room by squeezing it between my fingers, and two piles of cocktail sticks, one broken into small pieces but the other ‘full length’, as it were.
The point of these rather daft analogies was to demonstrate how actin might generate protrusive force in amoeboid motility. The cocktail sticks (and you can do the same thing with spaghetti or different lengths of copper wire, as in the above picture) showed my audience, I hope, that anything long and thin takes up more volume than the same mass of shorter ‘filaments’ of that thing.
What this has to do with amoeboid motility, and actin polymerization, is described in a paper from a collaboration between my previous boss in Cambridge and Tom Roberts at Florida State University, that is now available from PNAS. There will also be a short note about this finding in J Cell Biol (and I have discovered that there is a distressing lack of cell biologists in this building, so I have no one to skite to about it) sometime in the next week or two.
Briefly,
elongating filaments [contribute to] protrusion by generating an expansion of the cytoskeleton gel.
It’s all to do with packing volumes and aspect ratios, and there is a cute movie in the Supporting Information demonstrating what we mean.
The story of the paper itself is an interesting one. We sent it, two years ago, to a couple of ‘top rank’ journals because we believe that if it is not a paradigm, it is at least a new way of thinking about force generation in crawling cells. Unfortunately our manuscripts were savaged by cell biologists who essentially did not understand the physics, or by physicists who did not understand the biology: twice we had an incredibly hostile report and a quite favourable one.
At that stage we were quite frustrated because we accepted that we might be wrong in our conclusions, but were concerned that people were not getting the chance to test the hypothesis. None of the reviewers, it seemed, had any reasonable grounds for rejecting the work (the experiments were sensible and were done well, for example); it was mere prejudice against our experimental model that was keeping it back.
All our work was done with something called major sperm protein . This simple molecule is only found in nematode worms, and it, not actin, powers their sperm’s amoeboid crawling. It looks like actin-based crawling, it has similar kinetics and is based on polymerization, but it is not actin. It is much simpler, does nothing else in the cell that might interfere with motility, and appears to require fewer accessory factors. After we (that is the groups in Tallahassee and Cambridge) had been working on this for about ten years, we really were concerned that the actin guys were going to beat us to it.
The reviewers from PNAS however were favourable, and we were able to address their points and get the manuscript accepted. Now it is up to the rest of the world to tear it apart — I’m off to the pub. And there is no truth at all to the rumour that I was hired to place undue influence on Tom Pollard.
(And my catchphrase — I yearn to learn how the worm sperm turns — is now obsolete. Time to find another.)
L. Miao, O. Vanderlinde, J. Liu, R. P. Grant, A. Wouterse, K. Shimabukuro, A. Philipse, M. Stewart, T. M. Roberts (2008). The role of filament-packing dynamics in powering amoeboid cell motility Proceedings of the National Academy of Sciences, 105 (14), 5390-5395 DOI: 10.1073/pnas.0708416105
Well done on getting into PNAS! With such a moving story too.
Did the guy shut up when you hit him with the marble?
That’s a splendid thought, Bob. I shall bear it in mind next time I am heckled.
Even better:
“Recommend my paper for acceptance or I will ping this marble off your shining forehead.”