For researchers at the University of Wisconsin-Madison, creating their strongest collagen yet could pave the way for medical applications in wound healing, nanowires in medical devices, and artificial skin.
During the past decade, the researchers have been studying the fundamental structure of the collagen triple helix. Ron Raines, PhD, professor of biochemistry and chemistry at the university, likens collagen to DNA. Collagen, the most abundant protein in humans, is a helical structure made of multiple strands (three strands), while DNA is a double helix. The triple helix forms fibrils, which make up the structures of the human body.
Although the findings could lead to the development of artificial skin, funding stands in the way of moving research in this direction. Instead, Raines and his team are focusing on using the collagen for wound healing therapies. The process begins by taking the collagen-containing strands and anchoring them to another molecule that promotes healing.
“By studying this at a chemical level, we’ve come to a new understanding,” says Raines. “We can go into the amino acids that make up collagen and make very small subtle changes—for example, replacing a hydrogen atom with a fluorine atom. Another change is to replace a hydrogen atom with a methyl group, which is a carbon and three hydrogens.”
By making certain changes in the right place, the researchers learned how to make triple helices that are much stronger than anything nature makes, according to Raines. In a paper recently published in the Proceedings of the National Academy of Sciences, the researchers demonstrated what Raines calls the most stable triple helix ever made. They determined the 3-D structure of the collagen using x-ray crystallography, which allowed them to see every atom in the triple helix. From there, they observed that each atom was in the correct place—the same place in which they’re located in natural collagen. “We count this as a success, because we know that the collagen triple helix is much stronger, yet we also know that its structure is unchanged,” says Raines.
“In recent experiments that are just a few weeks old, we have some histological results demonstrating that we’re promoting wound healing in mice with this strategy. It’s very exciting,” says Raines. “If you define a device in a nanotechnology way, this is kind of a remarkable device, because we’re using intimate knowledge of chemistry and biochemistry and cell biology to promote wound healing at a molecular level.”
The next level of the research will be to show efficacy at the preclinical stage. The collagen, which is about 1–2 nm in diameter, would need to be integrated into a bandage or other material to deliver therapy.
Another aspect of the collagen research involves creating nanowires (about one micrometer) longer than anything found in nature, says Raines, for new sensing technologies. The wires, which are coated with a thin layer of gold to conduct electricity, are easier to modify than carbon nanotubes and could lead to detection devices. “Initially, we’re tethering molecules onto the collagen and then hoping and anticipating that the binding of natural receptors for ligands will alter the flow of electricity,” says Raines. “That could be the basis for some kind of feedback loop, which could be part of a medical device.” The sensors would detect changes in the flow of electricity. However, this research is in its very early stages.
“With the super strong technology, I think that we’re maxed out in terms of basic research,” says Raines. “I do not think, and I’ve learned a lot of about collagen, that it would be possible for us, or anybody, to make a stronger collagen than we just reported. I would be stunned if that were possible.” Using the long nanowires for sensing applications will be require more research and testing to find its most practical use.
The National Institutes of Health is providing research funding. Raines says that his team will be moving forward with further work involving both the collagen for wound healing and the nanowires for electronic medical applications.