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Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel–enzyme hybrids

Nature Chemistry volume 6, pages 511–518 (2014)Cite this article

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Abstract

Soft materials that exhibit stimuli-responsive behaviour under aqueous conditions (such as supramolecular hydrogels composed of self-assembled nanofibres) have many potential biological applications. However, designing a macroscopic response to structurally complex biochemical stimuli in these materials still remains a challenge. Here we show that redox-responsive peptide-based hydrogels have the ability to encapsulate enzymes and still retain their activities. Moreover, cooperative coupling of enzymatic reactions with the gel response enables us to construct unique stimuli-responsive soft materials capable of sensing a variety of disease-related biomarkers. The programmable gel–sol response (even to biological samples) is visible to the naked eye. Furthermore, we built Boolean logic gates (OR and AND) into the hydrogel–enzyme hybrid materials, which were able to sense simultaneously plural specific biochemicals and execute a controlled drug release in accordance with the logic operation. The intelligent soft materials that we have developed may prove valuable in future medical diagnostics or treatments.

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Figure 1: BAmoc–peptide hydrogels.
Figure 2: H2O2-response sensitivity of BPmoc–peptide hydrogels.
Figure 3: Oxidase⊂BPmoc-F3 hybrid gels.
Figure 4: Serial coupling of enzymatic reactions in the BPmoc-F3 hydrogel for expansion of a chemical-stimuli response.
Figure 5: Reduction-responsive hydrogel and its combination with enzymes.
Figure 6: AND or OR logic-gate response of supramolecular hydrogels encapsulating multiple enzymes.

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Acknowledgements

This work was supported in part by the JST (Japan Science and Technology Agency), the CREST (Core Research for Evolutionary Science and Technology) program, a Grant-in-Aid for Young Scientists (A) (No. 23681022), the Scientific Research on the Innovative Areas ‘Molecular Robotics’ (No. 25104512), the global Centre of Excellence program, ‘Integrated Materials Science’ of the Ministry of Education, Culture, Science, Sports and Technology (Japan). M.I. thanks the Tokuyama Science Foundation for financial support. We acknowledge Y. Chujo and N. Kitamura (Kyoto University) for allowing us to use the transmission electron microscope and for their support, K. Kuwata (Kyoto University) for high-resolution mass spectroscopy measurements, E. Kusaka (Kyoto University) for NMR measurements and M. Ichihashi and M. Wagatsuma (Initium, ULVAC) for quartz-crystal microbalance measurements. We thank E. Ashihara (Kyoto Pharmaceutical University) and Y. Takaoka (Kyoto University) for their help in taking blood samples. T.Y. acknowledges the JSPS (Japan Society for the Promotion of Science) Research Fellowship for Young Scientists.

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Authors and Affiliations

  1. Department of Biomolecular Science, Graduate School of Engineering, Gifu University, Gifu, 501-1193, Japan

    Masato Ikeda

  2. United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, 501-1193, Japan

    Masato Ikeda

  3. Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, 615-8510, Kyoto, Japan

    Tatsuya Tanida, Tatsuyuki Yoshii, Kazuya Kurotani, Shoji Onogi & Itaru Hamachi

  4. Department of Macromolecular Science and Engineering, Kyoto Institute of Technology, Matsugasaki, 606–8585, Kyoto, Japan

    Kenji Urayama

  5. Japan Science and Technology Agency (JST), CREST, 5 Sanbancho, Chiyoda-ku, 102-0075, Tokyo, Japan

    Itaru Hamachi

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Contributions

M.I., T.T., T.Y., K.K., S.O. and K.U. performed the experiments and M.I. and I.H. conceived the project. The paper was written by M.I. and I.H. and edited by all the co-authors.

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Correspondence to Itaru Hamachi.

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Ikeda, M., Tanida, T., Yoshii, T. et al. Installing logic-gate responses to a variety of biological substances in supramolecular hydrogel–enzyme hybrids. Nature Chem 6, 511–518 (2014). https://doi.org/10.1038/nchem.1937

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