Saturday, January 10, 2009

Mind over Matter

Alternate title: "Hardy Hair"

My mind gets blown pretty often these days. Here's why there's bit of it all over the place right now:

"A pilus (from the Latin word for 'hair') is a stiff protein appendage that is thinner than a flagellum and loks like a long hair projecting from the bacterium. A single bacterium may have only one pilus or up to hundreds of pili. The surfaces of some bacteria are covered with tiny protein fibrils referred to as fimbriae (from the Latin word for 'fringe'). Pili and fimbriae are hollow and are made up of repeating subunits of a protein called pilin. Like flagella, pili are assembled at their tips by passing the pilin subunits through the hollow core; the subunits are then assembled spontaneously at the pilus tip." (Walker, T. Microbiology, Philadelphia: W.B. Saunders Co., 1998, p. 29).

I remember learning about pili in biology, but I never thought about the fact that they were hollow. I had no idea what the function of these pili were (adhesion) and that the subunits could travel up through the hollow pili in order to extend it. This is amazing! For one thing, it just shows me that God is into details. But how'd He come up with this?

On the cellular scale, pili are long, heavy objects, and this thing would be a pain for the cellular construction workers to fully assemble, navigate through traffic with a "WIDE LOAD" sign, insert through the cell membrane, and hammer into place. So, pilin was made fully animated (or that's how my simple mind pictures it), and these subunits dance into place, traipsing through the hollow passage that God designed for them, singing "Heigh-ho, heigh-ho," and enjoying all the echoes.

After all, if there was no hollow passageway, how could a pilus be extended outside the confines of the cell membrane? Say that the pilin was to be packed tightly together, with no hollow passageway inside. The cell's the New York City of hubbub, and a pilus is needed to extend from the cell right outside downtown. So there's no room to preassemble it. But even if there was room, how would you extrude the completed pilus through the cell wall without comprimising the integrity of the intracellular environment? Rupturing the cell membrane is risky business: you don't want just any old molecule to diffuse into the cell, and you don't want any of your carefully selected molecules diffusing out without due process! It'd be the equivalent of us opening a 10-mile line of our border with Mexico!

Say the cell came up with the idea of assembling a closely-packed pilus (solid not hollow) "out of doors." That would solve the cell-integrity problem: just find a pilin exporter and insert it into the cell membrane. Import and export will remain as the highly regulated processes they should be. But a new problem emerges. How could you pump pilins out of the cell and expect them to find the pili they're supposed to be extending? That's pretty much equivalent to ejecting steel bars, nuts, and bolts from your spaceship and expecting them to assemble themselves into a rugged, linear structure. So you've got a dilemma: you either apply for a zoning permit to assemble the entire pilus in downtown New York City (and everybody knows just how willing the cellular beaucrats are going to be on that one) and push it through the cellular membrane, risking the homeland security of your entire cell, or you eject all your dearly-bought pilins out the front door and hope they find each other and self-assemble. Nice catch 22 you find yourself in.

I've got to say that building what I like to call a "straw wigwam" with my cousins really makes me appreciate what God pulled off with this whole pilus thing. It's not a trivial matter to plan the efficient delivery of materials to a worksite, let alone ensure that they interlock well enough that you don't have massive structural failures. And when my cousins and I were making our structure, we didn't have to worry about extending it into a hostile environment where any leak could signal the end of life as we knew it.

And that's why I think it's so easy to write off the design element in something so "simple" as a pilus. Since we've never had to design a pilus, we take the pili we stumble across for granted. Of course there's pili, and of course their subunits are shipped down through their hollow core as they assemble! How else would they be able to form?

Well, everything's simple once it's been proved, polished, published, and Powerpoint-presented to you. C'mon: my research isn't complicated; it's just that I haven't found the right answer yet! (Hold it -- that's why it is complicated: because dead ends are bold hussies and solutions are refined and elusive).

I truly think that if each of us who looked at biological systems had an engineering background, we'd be more likely to appreciate the solutions that a Master Designer presents to us free of charge, and fully optimized.

After all, I've been playing free and loose, and writing as if matter had a mind, and as if a cell could contemplate its navel. If a pilus didn't form properly, how could a cell tell its minions to "get back to the drawing board"? Sure, I know that "selection pressures" are the motivating factor in the idea of evolution. But selection pressures are just the boss with the power to hire or fire. The worker is the one who's got to innovate and come up with new concepts to try out. I know how inefficient trial and error can be for me, but how about the efficiency of a cell that has no capability of rational thought, one try before its "does or dies," no research notebook, no funding, no way of rallying undergrads and explaining the process and the approach, and no way to dig into the prokaryotic literature to see what past cells did in this situation of needing a pilus. (Which brings up another dilemma. Even if (and that's a stretch not even Mrs. Incredible could manage) a cell did hit on the idea of assembling pili by creating a hollow passage for pilin to toddle down, how could it communicate this to successive generations of cells? Ah, you say, it all depends on the structure of pilin: it can only self assemble to form a hollow structure. But how did a cell know that it needed to design a pilin that could form a hollow, interlocking structure? And remember, the structure of pilin is encoded in the cell's DNA. So it can't just play around with protein playdoh until it hits on the right structure, then send a memo to the DNA department that it should encode this structure in the DNA!

Forget the chicken and the egg. Did the pili protein, the RNA encoding it, the DNA encoding that, or the idea of assembling a hollow structure outside the cell come first? It was a hard enough question when it just came to the method. But now the issue of materials and two steps of templating comes into it!

Also, it opens the question that I've thought of before, but which I have no answer as of yet. What drives the movement of pilin down through the hollow pilus? And what drives them to interlock themselves into the pilus structure instead of diffusing away, or pointlessly bumping into one another: "'Scuse me" "Sorry" "Was that your eye?" "Uh, anybody got a match?" "If you knock me out again, I'm calling my lawyer!" More generally, what drives the intracellular movement of molecules? The shuttling of molecules through the cell membrane makes more sense to me, because it's often happening down a concentration gradient. But what causes a protein to glide into the nucleus of a eukaryote and start looking for that particular DNA strand it's supposed to bind? Is this, too, supposed to be caused by concentration gradients, or blind entropy? I know that proteins can navigate along the cytoskeleton, but still, that's not getting to the heart of the issue. WHY do molecules navigate along the cytoskeleton, or participate in what seems to be purposeful movement? I'm looking for casuation, and I don't have an explanation.

Directed molecular motion is intriguing to me, because molecules don't have minds. Though if they did, when they saw the complex motion and optimized, synchronized functions they carried out, their minds, like mine, might be blown too.

This world exists. We enjoy it, at least some of the time. Over eons could it have gradually developed to the level of complexity it's at now, or did it instantly snap into existence at the level of complexity it is now, like a DVD when you hit play?

That's the question, and you have until the end of the DVD to answer it for yourself.

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