Simple atomic switch makes for stronger collagen

Text by Evan Lerner

Collagen is the most abundant protein in the body. Named from the Latin for “glue,” its springy, tough coils are the main component of connective tissue, like ligaments and tendons, as well as of skin.

Collagen
By replacing a carbon and a hydrogen atom with a nitrogen atom at a key part of the protein, the Chenoweth group was able to add stabilizing hydrogen bonds.

Collagen is the most abundant protein in the body. Named from the Latin for “glue,” its springy, tough coils are the main component of connective tissue, like ligaments and tendons, as well as of skin.

Engineering collagen to be even tougher could form the basis of a variety of medical treatments, such as improved skin grafts and reconstructive surgery. But despite decades of research into collagen’s chemical composition, scientists have thus far been unable to modify the protein “backbone” to make it more resistant to unraveling.

Collagen
By replacing a carbon and a hydrogen atom with a nitrogen atom at a key part of the protein, the Chenoweth group was able to add stabilizing hydrogen bonds.

David Chenoweth, an assistant professor of chemistry in the School of Arts & Sciences, has succeeded where others have failed by taking a counterintuitive approach. Rather than adding atoms in hopes of creating new, stabilizing bonds, Chenoweth and lab members Yitao Zhang and Roy Malamakal achieved the effect by removing them, replacing a pair of atoms with a single one.

“The idea that a single atom replacement can make such a big difference was really what surprised us,” Chenoweth says.

The collagen protein is a repeating sequence of three amino acids, with every third unit the amino acid glycine. It self-assembles into a triple helix structure, with three strands wrapping around a hollow core. By devising a synthetic version of glycine that replaces a carbon and hydrogen atom pair with a nitrogen atom, the resulting “aza-glycine” was able to form more stabilizing hydrogen bonds in the interior of the collagen.    

“There are certain atoms in the inner section of collagen’s three strands, and some of those atoms have negative and positive polarity, sort of like magnets,” Chenoweth says. “So what used to be in there was like the negative pole of a magnet, but what was butting up against it was non-magnetic. We just replaced it with an atom that has a positive pole, and now the whole thing is a little stronger.”   

By replacing just the centermost glycine in a 21-amino-acid long collagen peptide, the researchers were able to get the triple helix to self-assemble quicker and maintain its structure longer when exposed to heat.

Because the replacement is part of collagen’s molecular “backbone,” it confers this extra stability without altering any of the surface features of collagen. That suggests it will be easier to incorporate into treatments, as the other biological interactions of the protein would remain unchanged.

The next steps for the Chenoweth lab include genetically engineering bacteria to produce this modified form of collagen, and exploring similarly structured biomolecules to see if they could be improved by the same kind of substitution.

Originally published on .