It is the most important structural protein in the body, reinforcing connective tissue, bones and teeth, and forming long, fibrous cables to strengthen tendons. Collagen forms sheets of tissue that support the skin and every internal organ. There is nothing in the body, in fact, that does not depend in some way on collagen.
In medicine, collagen from animals, principally cows, is used to rebuild tissue destroyed by burns and wounds. Commonly, it is employed in plastic surgery to augment the lips and cheeks of starlets and others seeking perpetual youth. Catgut, the biodegradable sutures made from cow or horse intestines and used in surgery to minimize scarring, is also a form of collagen.
But for such a commonplace and useful protein, collagen has defied the efforts of biomedical researchers who have tried mightily to synthesize it for use in applications ranging from new wound-healing technologies to alleviating arthritis. The reason: Scientists were unable to synthesize the human protein because they had no way to link the easily made short snippets of collagen into the long, fibrous molecules necessary to mimic the real thing.
But now a team of scientists from the University of Wisconsin-Madison, writing this week (Feb. 13, 2006) in the Proceedings of the National Academy of Sciences (PNAS), reports the discovery of a method for making human collagen in the lab.
The work is important because it opens a door to producing a material that can have broad use in medicine and replace the animal products that are now used but that can also harbor pathogens or spark undesirable immune responses. What’s more, the new work may also lay the foundation for applications in nanotechnology — such as microscopic sensors that could be implanted in humans to confront the effects of disease — because it gives scientists a way to precisely manipulate the lengthy molecules and add elements to collagen that confer new abilities.
"We can make collagen that duplicates nature exactly, but we can diverge from that when it is desirable," says Ronald T. Raines, a UW-Madison professor of biochemistry who, with postdoctoral fellow Frank W. Kotch, authored the new PNAS study.
Scientists have been seeking a way to make synthetic collagen for at least 30 years. In clinical settings, human collagen would be preferred over bovine collagen because the material now gleaned from cows can prompt an unwanted immune response in patients and it can harbor animal pathogens that might infect humans.
The Wisconsin team discovered a way to make the long, slender collagen molecules, in essence, by having the protein assemble itself. What was required, Raines explains, was a way to give the collagen snippets that scientists could easily make a way to "self assemble" into the long, thin fibers of native collagen. The Wisconsin team was able to modify the ends of the snippets so they could fit together and stick to form long collagen fibers.
"Now we can make synthetic collagen that’s longer than natural collagen," says Raines, who previously authored a paper in the journal Nature that demonstrated how to make synthetic collagen that is stronger than natural collagen. "We just don’t have to take what nature gives us. We can make it longer and stronger."
In medicine, synthetic human collagen could be used as "solder" to speed healing of large wounds. In the context of nanotechnology, collagen has appeal as a type of nanowire because it is thin — thinner even than the vaunted carbon nanotubes hailed by nanotechnologists — and long.
Coated with gold or silver, human collagen could form the basis of implantable electric sensors. By attaching certain biological molecules to the wire, it would be possible to create sensors that might, for example, quickly alert a diabetic to falling insulin levels. Similarly, equipped with molecules to recognize specific pathogens, such a sensor could stand perpetual guard in the body and provide instant warning of invading viruses or bacteria.
"We can have total control of what goes on these very thin extended fibers," says Raines. "We are able to build these molecules up one atom at a time and we can manipulate them in very precise ways."
The new Wisconsin study, which was supported by grants from the National Institutes of Health, lays a foundation for bringing human collagen to the clinic, says Raines. But he notes there is still some work to be done to perfect the technology.
For example, while the new work enables the researchers to make collagen molecules that are long and strong, ways to precisely control the self-assembly of collagen to molecules of a specified size remain to be worked out, according to Raines.
