Collagen, the most abundant protein in the body, has long been considered a predictable structural component of tissues. However, a new study led by Rice University challenges that notion, revealing an unexpected conformation in collagen's structure that could reshape biomedical research.
To explore collagen assembly at the atomic level, the research team designed a system of self-assembling peptides based on the collagen-like region of C1q, a key immune protein. They then used cryo-EM, a technology that allows scientists to visualize biomolecules with unprecedented detail, to analyze the structure of the assembled peptides. The resulting model revealed a deviation from the canonical right-handed superhelical twist.
"The absence of the superhelical twist allows for molecular interactions not previously observed in collagen," said Yu, a former graduate student of Hartgerink who is now a postdoctoral researcher at the University of Washington.
The implications of this discovery could extend beyond fundamental biology. Collagen is not just a structural protein, but plays essential roles in cell signaling, immune function, and tissue repair.
By gaining a deeper understanding of collagen's structural variability, researchers can unlock new insights into diseases where collagen assembly is compromised, including Ehlers-Danlos syndrome, fibrosis, and certain cancers.
Furthermore, this work lays the foundation for innovations in biomaterials and regenerative medicine. By harnessing the unique structural properties of this newly identified collagen conformation, scientists could design novel materials for wound healing, tissue engineering, and drug delivery.
Despite the ubiquity of collagen in human biology, studying its higher-order structures at high resolution has been a challenge. Traditional techniques, such as X-ray crystallography and fiber diffraction, have provided valuable insights but have not been able to capture the packing of collagen in complex assemblies. Cryo-EM, however, has overcome these limitations, allowing the research team to visualize the intricate architecture of collagen in new detail.