T he first time I handled a hagfish, I placed it none too gently in a pail two—thirds full of seawater. Within just a few minutes, the creature had become a hazy mirage at the bottom of three gallons of viscous slime.

Wonderful biomechanics were going on in that bucket, as the animal released a gel intended to discourage whatever might be harassing it. Watching the ooze, though, I never imagined that it would someday shed light on one of the most intriguing architectural problems in biology—the design and structure of the cytoskeleton, or cellular skeleton.

A hagfish is an unprepossessing creature.

A foot or so long, it bears a closer resemblance to a Coney Island frank than it does to a fish. It has a small mouth, surrounded by several short sensory structures called barbels, and it lacks both jaws and teeth. And as I demonstrated when I dropped one into the bucket, a hagfish can exude from its skin a substance so slimy and so plenteous it seems supernatural. After releasing the slime, the hagfish cleans off by tying itself in a knot that it then pulls itself through.

Hagfish slime is made up, in part, of proteoglycans—hydrated protein—and— sugar molecules that give all mucus its characteristic slippery texture. But more important for the question of cellular physics, the hagfish adds long, thin fibers to the mix. Taken together, those ingredients produce a slime reminiscent of what you might find under the noses of a classroom of preschoolers.

T o understand what any of this has to do with the cytoskeleton, it’s worth sketching what the cellular apparatus is and how it works. The model of the cell most of us learned in school was essentially a ball filled with a fluid (the cytoplasm) within which small bodies (the organelles) drift aimlessly. Cell biologists now know that a skeletal network of filaments permeates the cytoplasm—giving shape to the cell, anchoring its organellcs, and choreographing its internal actions.

The mechanics of the cytoskeleton depend in part on how its filaments react when a load is applied. Two kinds of filaments, known as microtubules and filaincntous actin, are stiff and strong. Both resist bending, stretching, and compression. Intermediate filaments (IFs), the third kind, seem much more flexible than the other two.

One line of evidence for that conclusion comes from studies done with transmission electron microscopes (TEMs). With a TEM you can make a stop—action image of a single slice of a cell. But how can a still image tell you anything about the flexibility of the filaments? Pasta may offer a useful analogy. Imagine two heaps of linguine, one cooked, the other dry. In any slice through the dry pile, the strands would show tip as straight lines. A slice through the cooked pile, though, would show many strands to be curved and curly. When cooked, a strand of pasta becomes more flexible, enabling its ends to move independently—hence the curves.

Filaments of the cytoskelcton are so thin they can be pushed around by the ran-dom movements, or so—called Brownian motion, of other, neighboring mole-cules. Those molecular forces and their effects on the filaments can be modeled mathematically, and the model shows that the more flexible the filaments are, the more they will look like the pile of cooked linguine. Combining such a model with TEM observations, the microtuhules seem to be 5,000 times stiffer than the IFs. By itself, that’s not entirely surprising: the microtubules are also thicker than the IFs. Yet even the filaments of filamnentous actin, which are thinner than the IFs, arc about twenty times stiffer.

So what accounts for the flexibility of the IFs?

Are their properties similar to those of cooked linguine? Not necessarily. Rope, for instance, only weakly resists bending or compression—yet, unlike linguine, it does a great job of resisting stretch. Ifs might be constructed of multiple molecular strands that slide past one another when bending, like the fibers of a rope. That’s where hagfish slime conies in: it’s an ideal system for testing whether Ifs act more like rope or like cooked linguine.

T he fibers of hagfish slime are made up almost exclusively of Ifs. Moreover, the long axis of each filament is aligned with the long axis of the fiber, making it plausible to think that the entire fiber acts like one filament writ large. On the basis of that assumption, Douglas. S. Fudge, a biologist at the University of British Columbia in Vancouver, reasoned that measuring the properties of slime fibers could help clarify the mechanics of IFs.

To test the properties of slime fibers, Fudge and his colleagues constructed a sensitive stretching machine. One end of a fiber was attached to a thin glass rod, just fifty microns in diameter. The other end was attached to a platform that could be slowly pulled away from the glass rod. By measuring the bend in the rod and how much the fiber stretched, Fudge was able to calculate the stiffness of the Ifs.

It turns out that the filaments are not very stiff at all, particularly when first stretched. That low initial stiffness, which is attributable to regions of the IFs known as terminal domains [see illustration below], is consistent with their wriggly appearance under the TEM. The low initial stiffness of IFs also suggests they give flexibility and elasticity to the cytoskeleton. Fudge found that an IF could he stretched by more than 30 percent and still rebound to its original length. If it was stretched much further, though, it would no longer spring back. Only if the filament was stretched by 100 percent would it snap.

That makes the structure of an IF unlike either rope or cooked linguine, but rather somewhat like a plastic six-pack holder with a heavy-duty rubber band attached to each end. If you pull gently on the rubber bands, they can stretch and recover their original length. But if you pull hard enough, the plastic holder stretches irreversibly and finally breaks apart.

Those properties could give the Ifs two roles inside cells. Stretched to less than their elastic limit (that is,less than 30 percent more than their original length), they could haul a cell hack into shape after a deformation. Stretching past that limit could serve as a mechanical signal that some region of the cell has been seriously deformed.

I am not surprised, in a general sense, that hagfish slime holds biomechanical secrets . Most genuine discoveries depend on broad knowledge that spans many levels of organization and design. So why shouldn’t the defensive goo of a fish in a bucket reveal the workings of a basic organizational component of all cellular life?

slime schematic

                                                                        ADAM SUMMERS


                                                                        is an assistant professor of ecology

                                                                        and evolutionary biology at the

                                                                        University of Califoirnia, Irvine.



October 2004. (Pgs. 38-9)

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