article published yes Carson C. Cole author Mark A.B. Kreutzberger author Kevin Klein author 1e7ede04-9e54-11f0-9ec4-8d4d5563c398 Kiana A. Cahue author Brett H. Pogostin author Adam C. Farsheed author Joseph W.R. Swain author Thi H. Bui author Arghadip Dey author Jonathan T. Makhoul author Marija Dubackic author Antara Pal author Ulf Olsson author Anđela Šarić author bf63d406-f056-11eb-b41d-f263a6566d8b0000-0002-7854-2139 Edward H. Egelman author Jeffrey D. Hartgerink author AnSa department 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; however, the principles guiding interhelical associations into higher-order structures remain unclear. Here, we incorporate cation−π and electrostatic charge pairs to probe interhelical interactions and elucidate the mechanisms driving triple helix assembly into fibrils, nanotubes, and nanosheets. Introducing cation−π pairs into a fibrillating collagen mimetic resulted in D-periodic fibrils with pH-sensitive gelation. By alternating the presentation of electrostatic and cation−π pairs, the assembly of another D-periodic fibril featuring inner and outer triple-helical layers was resolved by cryo electron microscopy to a resolution of 8 Å. At physiological pH, antiparallel association of these triple helices leads to the formation of nanotubes. 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. These self-assembling triple-helical peptides demonstrate how packing of higher-order structures can be tailored with supramolecular interactions and establish the relationship of different hierarchical collagen-mimetic assemblies as pH-dependent. American Chemical Society2026 eng 1526-460210.1021/acs.biomac.6c00345 2742956-2965 Cole, Carson C., Mark A.B. Kreutzberger, Kevin Klein, Kiana A. Cahue, Brett H. Pogostin, Adam C. Farsheed, Joseph W.R. Swain, et al. “Supramolecular Assembly of Collagen-Mimetic Eptide D-Periodic Fibrils and Nanoassemblies.” <i>Biomacromolecules</i>. American Chemical Society, 2026. <a href="https://doi.org/10.1021/acs.biomac.6c00345">https://doi.org/10.1021/acs.biomac.6c00345</a>. Cole, C. C., Kreutzberger, M. A. B., Klein, K., Cahue, K. A., Pogostin, B. H., Farsheed, A. C., … Hartgerink, J. D. (2026). Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies. <i>Biomacromolecules</i>. American Chemical Society. <a href="https://doi.org/10.1021/acs.biomac.6c00345">https://doi.org/10.1021/acs.biomac.6c00345</a> Cole, Carson C., et al. “Supramolecular Assembly of Collagen-Mimetic Eptide D-Periodic Fibrils and Nanoassemblies.” <i>Biomacromolecules</i>, vol. 27, no. 4, American Chemical Society, 2026, pp. 2956–65, doi:<a href="https://doi.org/10.1021/acs.biomac.6c00345">10.1021/acs.biomac.6c00345</a>. C. C. Cole <i>et al.</i>, “Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies,” <i>Biomacromolecules</i>, vol. 27, no. 4. American Chemical Society, pp. 2956–2965, 2026. Cole CC, Kreutzberger MAB, Klein K, Cahue KA, Pogostin BH, Farsheed AC, Swain JWR, Bui TH, Dey A, Makhoul JT, Dubackic M, Pal A, Olsson U, Šarić A, Egelman EH, Hartgerink JD. 2026. Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies. Biomacromolecules. 27(4), 2956–2965. Cole CC, Kreutzberger MAB, Klein K, et al. Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies. <i>Biomacromolecules</i>. 2026;27(4):2956-2965. doi:<a href="https://doi.org/10.1021/acs.biomac.6c00345">10.1021/acs.biomac.6c00345</a> C.C. Cole, M.A.B. Kreutzberger, K. Klein, K.A. Cahue, B.H. Pogostin, A.C. Farsheed, J.W.R. Swain, T.H. Bui, A. Dey, J.T. Makhoul, M. Dubackic, A. Pal, U. Olsson, A. Šarić, E.H. Egelman, J.D. Hartgerink, Biomacromolecules 27 (2026) 2956–2965. 217492026-04-19T22:07:46Z2026-05-06T05:43:44Z