Wonder Thread: UD Scientists Report First Protein With Collagen And Elastin-Like Domains

September 18, 1997

Five times tougher and 16 times more extensible than a human tendon, the leathery, yet amazingly stretchy collagen threads produced by marine mussels might someday suggest strategies for developing better artificial skin and other biomimetic materials, say University of Delaware researchers whose work appears in the Sept. 19 issue of Science.

Described as containing "the first known protein [with] both collagenous and elastin-like domains," byssal threads help mussels latch onto rocks, oil rigs, super-tankers and docks, the UD researchers say. Not surprisingly, mussels "create a major fouling problem on economically important surfaces exposed to the sea," says J. Herbert Waite, professor of marine biochemistry in UD's College of Marine Studies.

Byssal threads feature "a stiff tether" at one end and a "shock absorber" on the end protruding from the mussel foot, explains graduate student Kathryn J. Coyne, lead author of the Science article, along with postdoctoral research associate Xiao-Xia Qin and Waite. This gradual transition, from one material to another, gives byssal threads a surprising mix of properties.

"If a byssal thread were simply a stiff stick attached to an elastic tube, it wouldn't have an outside chance of surviving these relentless tidal beatings," Waite notes. "In fact, the collagen in byssal threads goes from being a stiff material, to something that's very stretchy--without any sudden transitions." It's not yet feasible to manufacture materials featuring such gradual transitions, Waite says. But, he adds, "It's fun to dream about versatile new materials for a whole host of products--from steel-belted radials to shoes, which must be soft and flexible, yet tough enough to pound the pavement." Waite emphasizes that his current work primarily provides fundamental insights into the molecular construction of byssal threads.

In the future, however, a better understanding of byssal threads might help scientists design biomaterials that take advantage of their remarkable properties, says Harold Slavkin, director of the National Institute of Dental Research, one of the National Institutes of Health, which sponsored the UD study. "Insight into the molecular structure that makes the byssus strong yet flexible might suggest, for example, new strategies for designing more comfortable and pliable artificial skin," Slavkin says.

Curious Forms of Collagen

To find out what makes byssal threads so special, Qin and Waite first isolated two key collagens: Col-P and Col-D. They used pepsin, an enzyme secreted by stomach cells of vertebrates, to pinpoint the collagens. Unlike most proteins, Waite says, Col-P and Col-D don't break apart in response to pepsin. Since pepsin works best in an acidic environment, researchers simply placed byssal threads and pepsin in a weak solution of acetic acid. "Col-P and Col-D were the only proteins detectable after pepsinization," Waite explains. "Within byssal threads, these two collagens are distributed in a complementary gradient, with Col-P predominant in the elastic, proximal region, near the foot of the mussel, and more Col-D at the far, or distal end."

The UD team also examined the protein precursors for Col-P and Col-D, found in the mussel foot, where byssal threads are produced. Specific antibodies--proteins designed to detect and fight off foreign molecules by binding with them--helped Coyne target preCol-P. First, messenger RNA (ribonucleic acid) containing the genetic code for the protein was extracted from mussel foot tissue. Next, RNA was converted to the more stable DNA (deoxyribonucleic acid) form and cloned into bacteria, which expressed the protein encoded by the mussel's RNA. Designer antibodies, produced by a laboratory animal injected with Col-P, quickly latched onto the protein precursor expressed by bacterial clones.

Three Major Domains

The preCol-P in byssal threads contains three major domains, Coyne says. The middle section of the protein precursor consists of a tough collagen-based domain, flanked on either side by a pair of elastin-like regions. These stretchy domains are then framed at each end by sections rich in the amino acid, histidine.

The rubbery sections of preCol-P resemble bovine elastin, which is "very similar" to human elastin, Coyne reports. "Elastins typically are found in the skin and arteries of vertebrate species only," she notes. "The presence of these types of sequences in proteins from an invertebrate species is unusual."

The elastin-like regions of preCol-P also contained high levels of glycine and alanine--the amino acids most prevalent in two forms of protein in spider silk, Waite says. Although the structural similarity between preCol-P and spider silk still must be verified, Waite says the possibility should interest biochemists. "Spider silk is so thin, it has been difficult for anyone but crystallographers to deal with it," he says. "Byssal threads could turn out to be an interesting substitute, or model for studying some aspects of spider silk."

Curiously, the collagenous regions of preCol-P contain a missing glycine. "When a deletion like this is found in other structural collagens," Waite says, "it's certainly lethal to the animal. So, it's quite fascinating to find a missing glycine in a perfectly functional collagen subjected to great stress and strain in marine environments." It's possible, Waite speculates, that the missing glycine creates a 35-degree "kink" or bend in the collagen. But, he adds, "how that might contribute to the stretchiness of the protein is anybody's guess."

Two histidine-rich domains, located at each end of preCol-P, may play a role in forming protein-zinc complexes, Qin says. Whenever histidine-rich domains occur in proteins, they usually bind with metal. In blood, for instance, histidine-loaded glycoprotein binds with zinc. In byssal threads, she says, these domains may react with metals to produce strong "bridges," which link up linear arrays of collagen. Breaks in some of these cross-linked sections appear to be promptly repaired, Waite says. "This is totally different from how vertebrate collagens form fibers in nature," he notes. "Bridge formation seems to be reversible, so that if you pull them apart, they reform when you bring them back into contact."

Biomedical or consumer materials based on byssal threads are "a long way off," Waite says, but the UD findings suggest some tantalizing possibilities. "What this study contributes, at this point, is a completely new way of looking at the potential properties of structural collagen--the human body's most abundant protein," he says.

University of Delaware

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