U of G biologist's studies of hagfish slime help point to new way of making elusive light-but-strong materials
BY ANDREW VOWLES
Hagfish would have been the last thing on Prof. Doug Fudge's mind when he was growing up and fishing for bluefin tuna with his father off the coast of Maine. Not that he would have been likely to snag one of the bottom-dwelling scavengers anyway. But pulling one of the primitive creatures from the Atlantic depths might have meant having to grapple with a slippery eel-like animal oozing copious amounts of slime from metaphorical head to toe — perhaps enough to have scared a youngster away from hagfish for life.
Today, the faculty member in the Department of Integrative Biology is studying not tuna but hagfish and, more specifically, how the revolting mess produced by these animals might help us understand more about our own cellular architecture and help us create some new biomaterials, including stronger-than-steel spider's silk.
Fudge became acquainted with hagfish and their slippery ways while studying biology at Cornell University in the early 1990s. Not actually fishes, they are classed along with lampreys. Lacking jaws and paired fins, they look like featureless lengths of fat brown garden hose with tapered tails and live on the ocean floor, including both east and west coasts of Canada.
Their signature attribute is an ability to churn out slime like no other creature on Earth. Poke at a hagfish in a pail, and within minutes you may see only the creature's distorted form through a gelatinous mix of slime and sea water. Lift the goop out of the bucket, says Fudge, and it's like holding a handful of slippery spider's webs — an apt description for another reason that will become apparent.
Hagfish secrete the stuff through special glands running the length of their body. Biologists believe it's produced as a defensive device, gumming up predators' respiratory systems and effectively choking them. (Fudge and other researchers at the University of British Columbia, where he completed his PhD, rigged up a fish head model to test the idea and found that water flow over slimed-up gills slowed to a trickle.)
Hagfish rid themselves of slime through a Houdini-like trick of knotting themselves and passing the knot down their body, scraping away the material.
What's a slimy mess to fishers trying to clean a boat deck has become a source of fascination for this Guelph biologist. In what sounds more like a materials science project than zoology, he's now studying the mechanical properties of the slime for possible applications in everything from human health to structural mechanics.
In late October, Fudge learned that his paper on the workings of hagfish slime will appear in the Journal of Experimental Biology. That paper actually returns to his initial research interest, work he'd begun for his doctorate before venturing down another track.
At UBC, he hadn't gone far with his slime biomechanics project before he saw that fibres contained in the slime might serve as a model for studying structures in the cellular scaffolding of all animals.
“Initially, I was interested in how slime works. Then I realized I was trying to figure out how the cytoskeleton works.”
Clicking through microscope photographs on his computer, he points out so-called intermediate filaments that lend the slime its substance. Normally coiled like balls of yarn, the filaments — finer than spider's silk — unravel when ejected and exposed to sea water. They turn out to be incredibly stretchy and can be pulled out taffy-like to three times their length before snapping. (Fudge shows off his custom-made cell stretcher resembling a ping-pong paddle with electronics in the handle and a filament for attaching tissue where the paddle should be.)
Scientists already knew that intermediate filaments exist in nearly all animal cells. They're part of a scaffolding system of rods and strands of varied shapes and sizes that make cells rigid yet flexible, holding the cell together and maintaining its shape. Related structures include contractile filaments of muscle fibres made by actin and myosin proteins — a research interest of Prof. John Dawson, Chemistry — and microtubules, or protein filaments involved in cell division.
“Each one of your cells, except for red blood cells, is held together by this elaborate network of filaments,” says Fudge.
Biologists had assumed that these intermediate filaments were stiff and inflexible. That assumption was challenged by a paper he had published in Biophysical Journal in 2003. He found that these filaments come in various forms (some 65 genes code for different structures) and that they bend and stretch in various ways.
To illustrate, Fudge reaches for a shelf in his Axelrod Building office and picks up what looks like a chemist's 3-D molecular model made of coloured wooden dowels, plastic straws and elastic bands. The colourful, flexible sphere is actually a model of a cell's cytoskeleton, complete with actin and myosin proteins (the straws), microtubules (the dowels) and flexible bands. Plucking at one of the bands, he says: “If cells are ‘tensegrity' structures, then intermediate filaments are the rubber bands that allow cells to deform but then revert to their initial state.”
Fudge says not all biologists agreed that intermediate filaments in cells behave this way. Acknowledging the skepticism — and even resistance — that the idea raised among cell biologists, he points to more recent results by a French scientist.
That researcher used an atomic force microscope to basically trace the 3-D contour of these “rubber bands” during stretching. His results matched what Fudge had found. “Now, cell biologists have to deal with the fact that intermediate filaments are stretchy,” he says. (His UBC team published another paper — in Proceedings of the Royal Society of London — about the structure and mechanics of harder tissues such as hair, nail, hoof and baleen based on intermediate filaments called alpha-keratins.)
Not only are these filaments stretchy, but it also turns out that stretching filaments from hagfish slime transforms them into a new material that's light but strong.
Tug on the plastic rings holding together a six-pack and you encounter initial resistance. Keep tugging and the material begins to loosen and deform. Do the same thing to these intermediate filaments and they actually snap into a new molecular conformation, one that looks and feels amazingly like spider's silk. And not just any old spider's silk, but the artificial stuff that scientists have been trying to develop for some two decades by isolating the pertinent genetic material from spiders and churning it out in vast amounts in goat's milk.
The goal: to develop a cheap, reliable source of silk that might have structural uses. Make a bulletproof vest out of spider's silk, for instance, and you've got a substance that's tougher per unit weight than nylon or other synthetic materials but cheaper and more environmentally friendly to make. Researchers have been stymied in their attempts to make the cloned material — partly, Fudge believes, because something in the “magic” of the spinning process or in the glands producing the silk dope can't be replicated in the genetically engineered version.
He and his UBC collaborators think they've found another way to make this “bio-steel.” Just this fall, they were awarded a patent for making silk-like fibres using intermediate filaments like the ones in hagfish slime. (His collaborators are working with the company pursuing the goat's milk solution.)
“The more we thought about it, the more excited we got,” says Fudge.
Earlier, he'd gotten excited about hagfish during his first stint as an undergraduate working at the Shoals Marine Laboratory, located among the Isles of Shoals off the coast of Maine.
“I fell in love with the place,” says Fudge, describing the island's gull rookery and the menagerie of creatures living in its intertidal zone. He still visits there in the summer to teach a science methods course.
“The biology of the site is incredible. It really is natural selection right in front of your eyes.”
He came to Guelph to study anatomy and biochemistry of bluefin tuna before heading to UBC for his doctorate. Returning to U of G this year, he's now exploring ideas for biomaterials collaborations with biochemists, physicists and biomedical scientists interested in everything from the mechanics of horse hooves to the structure of whale baleen. Further afield, he's working with a Scottish colleague studying mechanical properties of human cell filaments affected by a genetic mutation that causes a rare skin disorder.
Fudge lives in Guelph with his wife, Esta Spalding, a writer and co-editor of the Canadian literary journal Brick and a former English instructor at U of G. They have a two-year-old daughter, Gemma.
He will speak on “Slime, Cells and Silk: Comparative Mechanics of Intermediate Filaments” Nov. 10 at 2:30 p.m. in Room 241 of the Food Science Building, as part of the Centre for Food and Soft Materials Science's seminar series.
