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Parallel transmission in a synthetic nerve

Abstract

Bioelectronic devices that are tetherless and soft are promising developments in medicine, robotics and chemical computing. Here, we describe bioinspired synthetic neurons, composed entirely of soft, flexible biomaterials, capable of rapid electrochemical signal transmission over centimetre distances. Like natural cells, our synthetic neurons release neurotransmitters from their terminals, which initiate downstream reactions. The components of the neurons are nanolitre aqueous droplets and hydrogel fibres, connected through lipid bilayers. Transmission is powered at these interfaces by light-driven proton pumps and mediated by ion-conducting protein pores. By bundling multiple neurons into a synthetic nerve, we have shown that distinct signals can propagate simultaneously along parallel axons, thereby transmitting spatiotemporal information. Synthetic nerves might play roles in next-generation implants, soft machines and computing devices.

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Fig. 1: Design of a bio-inspired synthetic nerve.
Fig. 2: Rapid sensory transduction and directional transmission in a synthetic neuron.
Fig. 3: Electrochemical communication in a synthetic neuron.
Fig. 4: Parallel transmission in a synthetic nerve.

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Data availability

Data supporting the findings of this study are available within the paper and its Supplementary Information. Additional source data and design files that support these findings are available in the Figshare repository https://doi.org/10.6084/m9.figshare.17122127.v1. Alternatively, data are also available from the corresponding author upon reasonable request.

References

  1. Someya, T., Bao, Z. & Malliaras, G. The rise of plastic bioelectronics. Nature 540, 379–385 (2016).

    Article  CAS  PubMed  Google Scholar 

  2. Choi, S. et al. Highly conductive, stretchable and biocompatible Ag–Au core–sheath nanowire composite for wearable and implantable bioelectronics. Nat. Nanotechnol. 13, 1048–1056 (2018).

    Article  CAS  PubMed  Google Scholar 

  3. Lacour, S., Courtine, G. & Guck, J. Materials and technologies for soft implantable neuroprostheses. Nat. Rev. Mater. 1, 16063 (2016).

    Article  CAS  Google Scholar 

  4. Yang, X. et al. Bioinspired neuron-like electronics. Nat. Mater. 18, 510–517 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kim, Y. et al. A bioinspired flexible organic artificial afferent nerve. Science 360, 998–1003 (2018).

    Article  CAS  PubMed  Google Scholar 

  6. Wehner, M. et al. An integrated design and fabrication strategy for entirely soft, autonomous robots. Nature 536, 451–455 (2016).

    Article  CAS  PubMed  Google Scholar 

  7. Karbalaei Akbari, M. & Zhuiykov, S. A bioinspired optoelectronically engineered artificial neurorobotics device with sensorimotor functionalities. Nat. Commun. 10, 3873 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Kuhnert, L., Agladze, K. I. & Krinsky, V. I. Image processing using light-sensitive chemical waves. Nature 337, 244–247 (1989).

    Article  CAS  Google Scholar 

  9. Gizynski, K. & Gorecki, J. Chemical memory with states coded in light controlled oscillations of interacting Belousov–Zhabotinsky droplets. Phys. Chem. Chem. Phys. 19, 6519–6531 (2017).

    Article  CAS  PubMed  Google Scholar 

  10. Parrilla-Gutierrez, J. M. et al. A programmable chemical computer with memory and pattern recognition. Nat. Commun. 11, 1442 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Keene, S. T. et al. A biohybrid synapse with neurotransmitter-mediated plasticity. Nat. Mater. 19, 969–973 (2020).

    Article  CAS  PubMed  Google Scholar 

  12. Van de Burgt, Y. et al. Organic electronics for neuromorphic computing. Nat. Electron. 1, 386–397 (2018).

    Article  Google Scholar 

  13. Misra, N. et al. Bioelectronic silicon nanowire devices using functional membrane proteins. Proc. Natl Acad. Sci. USA 106, 13780–13784 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Amit, M. et al. Measuring proton currents of bioinspired materials with metallic contacts. ACS Appl. Mater. Interfaces 10, 1933–1938 (2018).

    Article  CAS  PubMed  Google Scholar 

  15. Lodish, H. et. al. Molecular Cell Biology 8th edn (W.H. Freeman, 2016).

  16. Pereda, A. Electrical synapses and their functional interactions with chemical synapses. Nat. Rev. Neurosci. 15, 250–263 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu, Y. et al. Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation. Nat. Biomed. Eng. 3, 58–68 (2019).

    Article  CAS  PubMed  Google Scholar 

  18. Keplinger, C. et al. Stretchable, transparent, ionic conductors. Science 341, 984–987 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. Yang, C. & Suo, Z. Hydrogel ionotronics. Nat Rev Mater 3, 125–142 (2018).

    Article  CAS  Google Scholar 

  20. Owens, R. M. & Malliaras, G. G. Organic electronics at the interface with biology. MRS Bull. 35, 449–456 (2010).

    Article  CAS  Google Scholar 

  21. Strakosas, X., Bongo, M. & Owens, R. M. The organic electrochemical transistor for biological applications. J. Appl. Polym. Sci. 132, 41735 (2015).

    Article  CAS  Google Scholar 

  22. Selberg, J., Gomez, M. & Rolandi, M. The potential for convergence between synthetic biology and bioelectronics. Cell Systems 7, 231–244 (2018).

    Article  CAS  PubMed  Google Scholar 

  23. Kim, C. Y. et al. Soft subdermal implant capable of wireless battery charging and programmable controls for applications in optogenetics. Nat. Commun. 12, 535 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Villar, G., Graham, A. D. & Bayley, H. A tissue-like printed material. Science 340, 48–52 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Booth, M. J. et al. Light-activated communication in synthetic tissues. Sci. Adv. 2, e1600056 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Holden, M. A., Needham, D. & Bayley, H. Functional bionetworks from nanoliter water droplets. J. Am. Chem. Soc. 129, 8650–8655 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Restrepo Schild, V. et al. Light-patterned current generation in a droplet bilayer array. Sci. Rep. 7, 46585 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Jones, G. et al. Autonomous droplet architectures. Artif. Life 21, 195–204 (2015).

    Article  PubMed  Google Scholar 

  29. Dupin, A. & Simmel, F. C. Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Nat. Chem. 11, 32–39 (2019).

    Article  CAS  PubMed  Google Scholar 

  30. Chow, B. Y. et al. High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463, 98–102 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yanoff, M. & Sassani, J. W. Ocular Pathology 8th edn 494 (Elsevier, 2020).

  32. Bada Juarez, J. F. et al. Structures of the archaerhodopsin-3 transporter reveal that disordering of internal water networks underpins receptor sensitization. Nat. Commun. 12, 629 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ernst, O. P. et al. Microbial and animal rhodopsins: structures, functions and molecular mechanisms. Chem. Rev. 8, 126–163 (2014).

    Article  CAS  Google Scholar 

  34. Bamberg, E. et al. Photocurrents generated by bacteriorhodopsin on planar bilayer membranes. Eur. Biophys. J. 5, 277–292 (1979).

    CAS  Google Scholar 

  35. Inoue, K. et al. Converting a light-driven proton pump into a light-gated proton channel. J. Am. Chem. Soc. 137, 3291–3299 (2015).

    Article  CAS  PubMed  Google Scholar 

  36. Huang, K.-S., Bayley, H. & Khorana, H. G. Delipidation of bacteriorhodopsin and reconstitution with exogenous phospholipid. Proc. Natl Acad. Sci. USA 77, 323–327 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ming, M. et al. pH dependence of light-driven proton pumping by an archaerhodopsin from Tibet: comparison with bacteriorhodopsin. Biophys. J. 90, 3322–3332 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bean, B. The action potential in mammalian central neurons. Nat. Rev. Neurosci. 8, 451–465 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Burnstock, G. Historical review: ATP as a neurotransmitter. Trends Pharmacol. Sci. 27, 166–176 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Soto, E., Ortega-Ramírez, A. & Vega, R. Protons as messengers of intercellular communication in the nervous system. Front. Cell. Neurosci. 12, 342 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Du, J., Hossain, Z. & Mandal, J. Protons: a neurotransmitter in the brain. Edorium J. Cell Biol. 3, 1–3 (2017).

    CAS  Google Scholar 

  42. Guerra-Gomes, S., Sousa, N., Pinto, L. & Oliveira, J. F. Functional roles of astrocyte calcium elevations: from synapses to behaviour. Front. Cell. Neurosci. 11, 427 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Tunuguntla, R. et al. Lipid bilayer composition can influence the orientation of proteorhodopsin in artificial membranes. Biophys. J. 105, 1388–1396 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yoshimura, K. & Kouyama, T. Structural role of bacterioruberin in the trimeric structure of archearhodopsin-2. J. Mol. Biol. 375, 1267–1281 (2008).

    Article  CAS  PubMed  Google Scholar 

  45. Graham, A. D. et al. High-resolution patterned cellular constructs by droplet-based 3D printing. Sci. Rep. 7, 7004 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Alcinesio, A., Krishna Kumar, R. & Bayley, H. Functional multivesicular structures with controlled architecture from 3D-printed droplet networks. ChemSystemsChem 4, e202100036 (2021).

  47. Jeong, D.-W. et al. Enhanced stability of freestanding lipid bilayer and its stability criteria. Sci. Rep. 6, 38158 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Preibisch, S., Saalfeld, S. & Tomancak, P. Globally optimal stitching of tiled 3D microscopic image acquisitions. Bioinformatics 25, 1463–1465 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work in the H.B. group (including C.E.G.H. and V.R.S.) is supported by a European Research Council Advanced Grant (SYNTISU). C.E.G.H. was also supported by Oxford’s Doctoral Training Centre for Synthetic Biology, which is funded by the Engineering and Physical Sciences Research Council and the Biotechnology and Biological Sciences Research Council (EP/L016494/1). Microbial rhodopsins were prepared by J.V. and a gift from the A. Watts Group (Department of Biochemistry, University of Oxford, funded by DSTL UK (DSTLX-1000099768)) and αHL the gift of I. Cazimoglu (Bayley Group, University of Oxford). We thank D. Lunn for discussions regarding the use of elastomer. We also thank A. Walter and Y. Tanaka (Tecella) for their assistance.

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C.E.G.H., V.R.S., and H.B. conceived the ideas behind the project, discussed the data and wrote the manuscript. C.E.G.H. (with assistance from V.R.S.) carried out the experiments and analysed the data. J.V. prepared the microbial rhodopsins.

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Correspondence to Hagan Bayley.

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Supplementary Figs. 1–31, Materials and Methods, theoretical considerations and references.

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Hoskin, C.E.G., Schild, V.R., Vinals, J. et al. Parallel transmission in a synthetic nerve. Nat. Chem. 14, 650–657 (2022). https://doi.org/10.1038/s41557-022-00916-1

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