Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies

Cole, C. C.; Kreutzberger, M. A. B.; Klein, K.; Cahue, K. A.; Pogostin, B. H.; Farsheed, A. C.; Swain, J. W. R.; Bui, T. H.; Dey, A.; Makhoul, J.; Dubackic, M.; Pal, A.; Olsson, U.; Saric, A.; Egelman, E. H.; Hartgerink, J. D.

doi:10.1101/2025.02.15.637692

bioRxiv · 10.1101/2025.02.15.637692

Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies

Cole, C. C.·Kreutzberger, M. A. B.·Klein, K.·Cahue, K. A.·Pogostin, B. H.·Farsheed, A. C.·Swain, J. W. R.·Bui, T. H.·Dey, A.·Makhoul, J.·Dubackic, M.·Pal, A.·Olsson, U.·Saric, A.·Egelman, E. H.·Hartgerink, J. D.

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Abstract

The collagen triple helix assembles hierarchically into bundled oligomers, solvated networks and fibers. Synthetic peptide assemblies, driven by supramolecular interactions, can form single triple helices through intrahelical amino acid pairs, but the principles guiding interhelical associations into higher-order structures remain unclear. Here, we incorporate cation-{pi} and electrostatic charge pairs to probe interhelical interactions and elucidate the mechanisms driving triple helix assembly into fibrils, nanotubes, and nanosheets. Introducing cation-{pi} pairs into a fibrillating collagen mimetic resulted in D-periodic fibrils with pH-sensitive gelation. Modifying the presentation of interhelical interactions also enabled the characterization of another D-periodic fibril resembling cartilage collagens, featuring inner and outer triple helix layers. Enhancing electrostatic charge pairs promoted antiparallel assembly, leading to the formation of nanotubes and nanosheets. The packing behavior of triple helices correlates with the interhelical interactions, where parallel associations favor fibril formation, and antiparallel interactions drive nanotube and nanosheet assembly.

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Cole, C. C., Kreutzberger, M. A. B., Klein, K., Cahue, K. A., Pogostin, B. H., Farsheed, A. C., Swain, J. W. R., Bui, T. H., Dey, A., Makhoul, J., Dubackic, M., Pal, A., Olsson, U., Saric, A., Egelman, E. H., Hartgerink, J. D.. 2025-02-16. Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies. https://doi.org/10.1101/2025.02.15.637692

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