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High-entropy non-covalent cyclic peptide glass

Nature Nanotechnology (2024)Cite this article

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Abstract

Biomolecule-based non-covalent glasses are biocompatible and biodegradable, and offer a sustainable alternative to conventional glass. Cyclic peptides (CPs) can serve as promising glass formers owing to their structural rigidity and resistance to enzymatic degradation. However, their potent crystallization tendency hinders their potential in glass construction. Here we engineered a series of CP glasses with tunable glass transition behaviours by modulating the conformational complexity of CP clusters. By incorporating multicomponent CPs, the formation of high-entropy CP glass is facilitated, which—in turn—inhibits the crystallization of individual CPs. The high-entropy CP glass demonstrates enhanced mechanical properties and enzyme tolerance compared with individual CP glass and a unique biorecycling capability that is unattainable by traditional glasses. These findings provide a promising paradigm for the design and development of stable non-covalent glasses based on naturally derived biomolecules, and advance their application in pharmaceutical formulations and smart functional materials.

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Fig. 1: Characterization of CP glass formed using a single component—cPY.
Fig. 2: Molecular mechanism underlying the formation of cPY glass.
Fig. 3: Tunable glass transition behaviours.
Fig. 4: Formation and characterization of HECP glass.
Fig. 5: High-entropy-enhanced mechanical properties of CP glasses.

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Data availability

All data are available in the article and its Supplementary Information. Source data are provided with this paper and are also available via Figshare at https://doi.org/10.6084/m9.figshare.26181884 (ref. 60). Additional requests can be directed to the corresponding author.

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Acknowledgements

This work was supported by the National Science Fund for Distinguished Young Scholars of China (no. 22025207 to X.Y.), the National Natural Science Foundation of China (nos. 22172172 and 22372174 to C.Y.; 22232006 to X.Y.; and 22372173 to P.Z.), National Key R&D Program of China (2023YFA0915300 to X.Y.), Youth Innovation Promotion Association of CAS (grant no. 2022049 to C.Y.) and the IPE Project for Frontier Basic Research (grant no. QYJC-2022-011 to C.Y.). Allocations of computer time from the Supercomputing Centre and ORISE system in the Computer Network Information Centre, Chinese Academy of Sciences, are gratefully acknowledged.

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Authors and Affiliations

  1. State Key Laboratory of Biochemical Engineering, Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China

    Chengqian Yuan, Wei Fan, Peng Zhou, Ruirui Xing, Shuai Cao & Xuehai Yan

  2. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, China

    Ruirui Xing & Xuehai Yan

  3. Center for Mesoscience, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China

    Xuehai Yan

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Contributions

X.Y. and C.Y. developed the concept of high-entropy non-covalent glass and designed the experiments. C.Y., W.F. and S.C. performed the experiments. C.Y., W.F., R.X. and X.Y. analysed the experimental data. P.Z. and C.Y. designed the theoretical model and performed the simulations. C.Y. and X.Y. wrote the paper. All authors discussed the results and commented on the paper.

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Correspondence to Xuehai Yan.

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Nature Nanotechnology thanks Mustafa Guler, Zigang Li, Ziyu Lv and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Multicolor emission of cPY glass.

a, Bright-field and fluorescent imaging of cPY glass. All the scale bars are 100 μm. b, Solid-state fluorescence spectra of cPY glass. c, Solid UV-Vis spectra of cPY glass. The UV-Vis absorption spectra of cPY glass demonstrated spike-like absorbance with four peaks at 319 nm, 370 nm, 478 nm, and 517 nm in the range from 300 nm to 800 nm, characteristic of the quantum-confined photoluminescence, revealing the presence of multiple CPs clusters with different sizes in the cPY glass.

Source data

Extended Data Fig. 2 Versatile HECP glass integrated with other functional components.

a, fluorescence spectra of HECP glass doped with two typical organic dyes. The emergence of the characteristic fluorescence peak confirms the successful introduction of dyes into HECP glass. The inserted images demonstrate the bright-field (top), POM (middle), and fluorescent imaging (bottom) of doped HECP glass. All the scale bars are 500 μm. b, Modulated conductivity of HECP glass doped with different concentrations of phytic acid (PA). Data are displayed individually (hollow dots) and as the mean ± s.d. from n = 3 independent measurements. c, Magnetic HECP glass achieved through the incorporation of Fe3O4 nanoparticles (NPs).

Source data

Extended Data Table 1 A summarized list showing classification criteria of different CPs types with varied glass-forming ability in this work
Full size table
Extended Data Table 2 A summarized list showing several crucial thermodynamic parameters for the formation of HECP glasses
Full size table

Supplementary information

Supplementary Information

Supplementary Figs. 1–51 and Tables 1–4.

Supplementary Video 1

AAMD simulations for the formation of cPY glass. This video illustrates the dynamic transition from a long-range ordered cPY crystal to a long-range disordered cPY glass. During the heating process, the temperature was increased from 300 to 590 K over 58 ns, causing the crystal structure to collapse due to the disruption of ordered hydrogen bonding and aromatic stacking interactions. This disruption leads to the formation of a supercooled liquid composed of various cPY clusters. The supercooled liquid was then held at 590 K for 40 ns to reach equilibrium. Following this, it was rapidly quenched to 300 K within 58 ns, thereby kinetically preserving the disordered conformers and resulting in the formation of glass. The aromatic groups are represented by red sheets. Hydrogen, nitrogen and oxygen atoms are coloured white, blue and red, respectively, whereas carbon atoms in the aromatic rings and other sections are coloured purple and green, respectively.

Supplementary Video 2

Magnetic HECP glass bead. This video demonstrates that the HECP glass bead, when incorporated with Fe3O4 nanoparticles (NPs), can be easily attracted by a magnet. This is in contrast to the pristine HECP glass bead, which exhibits no magnetic response. These observations clearly demonstrate the successful integration of a magnetic component into the HECP glass.

Source data

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Source Data Fig. 2

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Source Data Fig. 3

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Source Data Fig. 4

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Source Data Fig. 5

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Source Data Extended Data Fig./Table 1

Statistical source data.

Source Data Extended Data Fig./Table 2

Statistical source data.

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Yuan, C., Fan, W., Zhou, P. et al. High-entropy non-covalent cyclic peptide glass. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01766-3

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