An assistant scientist at UW-Madison has a developed new design strategy for creating much more stable synthetic collagen, a previously difficult task.
I. Caglar Tanrikulu is an assistant scientist in the laboratory of professor Ronald Raines and lead author of the study published in “Nature Chemistry.” Tanrikulu has been exploring ways to produce collagen chemically, and in the process, he realized something crucial: The structures must be symmetric.
Collagen is a protein found in bones, muscles, skin and tendons. It is a critical component of connective tissues, which hold the whole body together, providing support and strength.
“Imagine collagen [strands] like a thread almost … when three of these things come together, they sort of wrap around, like into a rope,” Tanrikulu said.
According to Tanrikulu, in this analogy, a thread is a protein strand, and a rope is made up of three threads wound together. For example, he explained that when the body makes skin, these “ropes” tie together into thicker bundles.
“Individual fibers may not be that strong, but when they come together, they are quite strong,” Tanrikulu said.
With complex structures, strength and stability are important. The human body naturally makes collagen, but scientists have been unable to find the right technique for creating it, until now. Symmetry, a seemingly simple solution, was not immediately clear to Tanrikulu, whose previous background was not in this specific field of biomaterials engineering.
“My background was in computational biology and molecular biology … I made proteins and I examined proteins … I had all the design ideas but I didn’t have chemical tools - chemical expertise - to actually make these peptides initially. So, I spent a lot of time thinking of how best to make these,” Tanrikulu said.
Collagen has a triple helix structure that is difficult to replicate while maintaining stability, Tanrikulu explained. Not only is each individual strand very long, causing multiple unwanted folds, but two other strands must be made for the structure to be complete.
Since creating long triple helices was too difficult, Tanrikulu worked with shorter peptides, chains of amino acids that comprise proteins.
While working with peptides interconnected with charge pairs to form the desired triple-helical structures, he noticed something no one else had before. In order to be stable, the structures must abide by specific rules of symmetry.
Much like a tessellated floor tile pattern, only the unit cell and the transformative symmetry rules must be known. Additionally, only certain peptides, however, are able to transform symmetrically.
Designing his peptides symmetrically, he was able to take one peptide and apply a symmetry transformation to it to ultimately describe the whole triple-helical fiber, successfully creating a synthetic collagen nanofiber.
“For these fibers to be stable … every peptide has to feel the same environment, every peptide has to have exactly the same interactions, every peptide has to be positioned at the same location with respect to other peptides,” Tanrikulu said.
This symmetry allows for strength. Without it, Tanrikulu explained that unsatisfied interactions result in lower stability and bundling of fibers, making the structures difficult to work with.
Now that he has shown the proof of concept, Tanrikulu hopes his technology will lead to biomedical benefits. According to Tanrikulu, some possible applications could include using these guidelines for creating collagen for use in cell cultures or in surgery.
