“I’ve had it with this hunting lark. There I am, swimming around, when up comes this tasty-looking fish – you know, one of those thin wiggly ones that slip down a treat. ‘Hmm, nice snack,’ I think, so I open my mouth and try for a bite. Big mistake. Next thing I know, I’ve got a gobful of mucus. It’s enough to make a shark sick. Still, you should have seen what happened to the next guy who tried it. Very nasty…”
EVEN if you’re the wiliest predator with a mouthful of super-sharp teeth, your prey isn’t always handed to you on a plate. Especially if you are foolish enough to have a go at a hagfish – an eel-like scavenger with one particularly anti-social habit. “These guys are the super-athletes of slime production,” says Douglas Fudge, a graduate student in the zoology department at the University of British Columbia in Vancouver. “Throw a medium-sized hagfish into a five-gallon bucket and annoy it sufficiently – grab it or stress it out in some way – and it can turn pretty much all the water in the bucket to slime. Almost instantaneously.”
There’s nothing like a mouthful of sticky mucus to put a predator off its dinner, so five gallons of the stuff makes a pretty formidable defence. Nor is it any old goo – the stuff that hagfish secrete is the bulletproof vest of the slime world, a super-tough mixture of clingy mucus laced with thin, yet strong fibres.
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It’s an extraordinary material, and Fudge has spent two years studying how hagfish create the stuff. He is particularly fascinated by the fine fibres that run through it. On the face of it, these fibres are similar to threads of silk. Like silk, they’re thin and extremely tough, but they appear to be made in a completely different way. If Fudge can unpick the secrets of this sticky tangle, he could pave the way for new super-strong materials that outperform the best in the business.
To hunt for clues, Fudge and his supervisor John Gosline have looked at how hagfish produce their suffocating slime. Most fish release small quantities of mucus, which helps to protect their scales and aids movement through the water. This goo starts life as tiny packets of dehydrated glycoproteins called mucins that are released from specialised cells in the fish’s skin. The moment these packets hit seawater, they burst open. The mucins absorb water and swell to produce strands of clingy mucus. But most fish release just a teaspoonful at a time. How can a hagfish squirt out such a flood on demand?
Part of the answer, says Fudge, has been known for about a century. Each hagfish has around 150 slime glands dotted along its sides. Here, the two raw materials for the slime – dehydrated mucins and fibres – are packaged and stored until they are sent into action. The mucins are stowed inside microscopic vesicles which are then packed into large granules. Meanwhile, the fibres are coiled up and stowed in oval sacks called thread cells.
When a hagfish gets riled, it simply squeezes the contents of its glands – about five grams of slime “concentrate” in all – into the sea. Immediately, water floods into the granules and their delicate walls rupture, releasing thousands of tiny mucin-packed vesicles. Then the vesicles start to split open and the mucins begin to swell. “When the whole mess hits the seawater, the mucin vesicles hydrate incredibly rapidly,” says Fudge. “It’s almost instantaneous, which is one of the things we’re really interested in.”
No one knows exactly how the mucus expands so quickly, but Fudge and Gosline think that it might behave something like the mucus secreted in our lungs and intestines. When mucin vesicles are released in our bodies, not only do they absorb water, but the mucin chains explode out of the vesicles like microscopic jack-in-the-boxes. At the end of each mucin protein is a negatively charged carbohydrate group. When these groups are squeezed together in a vesicle, the charges repel each other. However, each vesicle also contains a high concentration of positively charged calcium ions. These tiny ions can sit easily in the space between the carbohydrate groups. Since each calcium ion has two positive charges, they are very effective at neutralising the negative charges on the mucin chains, allowing the proteins to pack together tightly. But the moment the vesicles meet the water, sodium ions flood in and replace the calcium ions. Sodium ions have a single positive charge, and each ion is about five hundred times less effective at shielding than a calcium ion. Suddenly, the negatively charged carbohydrates can feel each other. “You remove the shielding and the negative charges start repelling each other like crazy,” says Fudge. The result is an explosion of sticky mucus.
Last year, Fudge and Gosline found that the vesicles in hagfish mucus also contain a high concentration of positively charged calcium ions. So the same mechanism could be at work in both human and hagfish mucus.
Events are no less violent in the thread cells. These cells are a remarkable feat of biological engineering: each intact cell contains a single fibre about a micrometre across but more than half a metre long. To pack it all into a space just 100 micrometres across, the fibre is coiled into an amazing structure the shape of a rugby ball. “When the cell is mature, this takes up 99 per cent of the room,” says Fudge, “the nucleus is tucked away in one corner of the cell and the rest is one continuous, coherent fibre.” But the moment that seawater gets into them, the ends of the tightly coiled thread pop out and the rugby ball begins to unravel.
Now things become very messy. Thread cells, mucus and mucin vesicles are all mixed up together. As the ends of the fibres snake out, they get caught in lumps of swelling mucin that surround them. Simultaneously, the mucin absorbs more and more water. So as it puffs up, it pulls the fibres with it. In seconds, the mucins have expanded more than a thousandfold, transforming into huge globs of tangled mucus, criss-crossed by a web of fine threads (see Diagram).
In fresh slime, these fibres are fairly evenly dispersed. “They’re almost invisible to the naked eye,” says Fudge. “It’s only when you reach into it that you realise that it’s more than just mucus.”
To a hungry predator hoping to dine on a hagfish, this stuff is a death trap. If it is unlucky enough to get caught up in the mucus, it will thrash desperately about, pulling and stretching the goo. As this happens, the fibres begin to tangle, twisting together into thicker, multi-stranded cables almost a millimetre across. “The more something struggles within it, the tighter it becomes,” says Gosline. This unbreakable noose draws tight around the fish’s body and thick strands of mucus start to clog its mouth and gills. Starved of oxygen, the fish begins to suffocate.
These fibres could also have a more subtle role to play. In 1991, Elizabeth Koch and Robert Spitzer, biologists at the Chicago Medical School in Illinois, suggested that the thin filaments control the properties of the mucus around them, and that they may even contribute to the incredible speed at which it expands. In experiments on a fresh slime-fibre mix, they found that as the threads uncoil, the mucin and mucin vesicles bind to them. This, the researchers suggested, helps to prevent the mucins and vesicles clumping together, increasing the surface area in contact with the water and speeding up the expansion of the mucus.
Fudge, however, remains unconvinced. “There’s obviously an interaction,” he says, “the fibres are acting as anchoring sites for the mucin, but I think it’s the other way round – the swelling of the mucus is pulling the fibres apart.”
Whatever the detailed mechanism, there’s little doubt that the fibres have a major impact on the mechanical properties of the fully developed slime. They act as a scaffold, trapping the lumps of water-bloated mucus and holding them together. “If you don’t have the fibres in there, it’s a liquid,” says Fudge. “You can stir it. The mucus is free to move any which way.” But with both mucus and fibres together, you’ve got a cohesive, strong, stringy slime that you could pick up in one piece – if you really wanted to.
Fudge has no problem getting his hands into this revolting stuff – “I’m past that now,” he says. To ensure a steady supply for their studies, Fudge and Gosline even have their own Pacific hagfish “herd” which they “milk” whenever a sample is needed. In fact, Fudge thinks that hagfish are ideally suited to life in a lab aquarium, despite their less than wholesome habits. Hagfish are ghoulish creatures that feast on the dead, the weak and the dying. They make a beeline for wounds or soft flesh and eat into them with extending “jaws”. Then they wriggle their way inside to chomp on the liver – a particular favourite – or any organ within reach. By the end of the meal, all that’s left of the victim is an empty bag of skin and bones. “Since they’re scavengers, they can go for ages without feeding,” says Fudge. Every few weeks, you simply drop some food in their vicinity. “They just crank up their metabolism and eat like crazy.”
Milked for mucus
Milking time is painless too. Fudge plops a hagfish into a bucket of water with a little anaesthetic added. When the fish is out cold, he lifts it from the water and uses an electrode attached to a low-voltage power supply to stimulate one or two slime glands. When the slime concentrate is collected safely in a dry test tube, Fudge puts the hagfish back in its aquarium to sleep off the experience.
One of Fudge’s main aims is to isolate individual fibres from the slime, but this has proved exceptionally tricky, since the fibres are so thin and tangled. But last year he managed to extract some and test their strength and toughness in the lab. “In terms of the amount of energy they can absorb without breaking,” he says, “they are pretty incredible.” Their mechanical properties could even rival those of another exceptional biopolymer, spider silk. If other tests confirm this, Fudge and Gosline could be on to something very important indeed.
Despite decades of study, spider silk is still a mystery. Each silk fibre has an extremely complex structure, with a central protein core wrapped in concentric layers of fine threads called nanofibrils. Chemists believe that these ordered nanofibril layers give silk its remarkable properties. No one, however, has been able to recreate this complex structure in the lab. So far the best artificial silks are only half as strong as the real thing (New Scientist, 24 April 1999, p 38).
Hagfish fibres, on the other hand, seem to have a much simpler structure. When Koch and Spitzer examined freshly secreted fibres they found that each one is made from about 800 fine threads lying approximately parallel to each other along the fibre. Interspersed among these threads are more than half a dozen microtubules, thin protein filaments found in almost every animal cell.
If the structure of hagfish fibres is as simple as the researchers suspect, they could be looking at a remarkable material – something that could eventually be woven to make ultra-strong fabrics and which should be more environmentally friendly to produce than the toughest artificial fibres such as Kevlar. “We think the hagfish fibres are quite a lot simpler than silk,” says Fudge, “and they should be a lot simpler to produce in the lab.”
Christopher Viney, a chemist at Heriot-Watt University in Edinburgh, agrees: “Lets say you’re going to make it in quantity by genetically engineering bacteria,” he says. “The simpler the molecule you have to make, the easier it will be.” Viney knows the problems of making artificial silk only too well. He has spent years studying how the material is made in nature. “If it’s simpler than silk,” he says, “then it is good news.”
Even if scientists eventually succeed at producing hagfish fibres in the lab, they’ll never be able to copy all of the hagfish’s tricks. Say you’re a hagfish and you’ve just slimed an ugly-looking predator. That puts you right in the middle of a slimy cocoon of your own making. So you’re stuck, right? Wrong. Hagfish have developed a neat strategy to get out of their own trap. “What they do is tie themselves in a knot and pass the knot down their body,” says Fudge. They may have to do it a couple of times, but this slick trick seems to wipe even the gooiest slime off their skin. “If you can’t tie yourself in a knot,” says Fudge, “then you’re in trouble.” Now find a scientist who can do that.
- Further reading: Keratin-like components of gland thread cells modulate the properties of mucus from hagfish, by E. A. Koch, R. H. Spitzer and others, Cell & Tissue Research, vol 264, p 79 (1991)
- Douglas Fudge’s website is at: www.zoology.ubc.ca/labs/biomaterials/slime.html