Abstract
The intertwined strand arrangement in ropes, from micro- to macro-scale, results in tensile moduli significantly higher than those of single strands. Micro-scale ropes are found in biological systems, most commonly in mechanically-rigid collagen tri-strand arrangements. While human-made macro-ropes possess either left-handed (S) or right-handed (Z) twist, collagen exclusively adopts Z-twist architectures. Despite its natural abundance, the reconstruction and control of these supramolecular ropes in biomimetic systems using minimalist building units remains a fundamental challenge. Here, we demonstrate that cyclo-tryptophan-proline dipeptide stereoisomers self-assemble into complex crystalline supramolecular triple-helical structures. These unique architectures display tunable S- or Z-micro-rope-like twists governed by the configuration of tryptophan residues, as confirmed by co-assembly experiments and molecular dynamics simulations. Tensile testing revealed that these supramolecular micro-ropes exhibit significant moduli. These findings provide a potential platform for designing biomimetic functional helical materials with tunable supramolecular chirality and mechanical strength using minimalist building blocks.
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Data availability
All data are available from the corresponding author upon request. Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2465098-2465101, 2465116-2465121, 2465132, and 2504998. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.
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Acknowledgements
This work was supported in part by the ISF—Israel Science Foundation by Grant no. 3246/23 within the China-Israel Cooperative Scientific Research (Grant No. 52361145848), Twin2pipsa—Twinning for excellence in biophysics of protein interactions and self-assembly grant (101079147). G.W. and B.X. acknowledge financial support from the National Natural Science Foundation of China (Grant Nos. 12374208 and T2322010) and the Natural Science Foundation of Shanghai (Grant No. 22ZR1406800). R.Y. thanks Natural Science Foundation of Shaanxi Province (Grant No. 2020JCW-15). P.-A.C. and D.T. thank Science Foundation Ireland (SFI) for financial support under Grant Number 12/RC/2275_P2 (SSPC). L.A.-A. acknowledges the support of the European Research Council (ERC), under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 948102), and the Israel Science Foundation (grants no. 2422/24). We wish to thank Dr. Davide Levy for PXRD measurements, Dr. Evelina Nikeshparg for assisting with the Raman measurements. Lastly, we are grateful to all members of the Gazit group for their insightful discussions and valuable input.
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H.Y., E.G., and R.Y. developed the concept of S- and Z-twist supramolecular micro-ropes by peptide stereoisomers. H.Y. conducted the peptide crystallization, materials characterization, and data analysis. S.S. carried out the solubility, HPLC, and NMR measurements. A.L., Y.D., T.P.J.K., and L.A.-A. performed time-lapse optical microscopy measurement and analyzed the data. C.Y. crystallized the O-P amino acid and conducted TGA and DSC measurements. J.S. and D.K. conducted the IR and VCD measurements. L.J.W.S. performed the single-crystal diffraction measurement and solved the crystal structures. Z.Y., Z.W., Y.T., and G.W. performed the all-atom single-crystal molecular dynamics and drafted the simulation part of the manuscript. B.X., T.L., W.S., and Y.C. measured the tensile modulus and Young’s modulus and analyzed the data. H.Y. drafted the manuscript, while E.G., R.Y., B.X., G.W., Y.C., D.T., S.R.-L., T.P.J.K., D.K., L.A., Y.C., and P.A.C. revised it. All authors provided feedback on the manuscript.
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Yuan, H., Yang, Z., Yuan, C. et al. Formation of S- and Z-twist supramolecular micro-ropes by peptide stereoisomers. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71043-5
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DOI: https://doi.org/10.1038/s41467-026-71043-5
