The use of graphene-based materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene’s peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that single-layer graphene increases neuronal firing by altering membrane-associated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene–ion interactions that are maximized when single-layer graphene is deposited on electrically insulating substrates are crucial to these effects.

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We thank M. Lazzarino, S. Dal Zilio and the Facility of NanoFabrication of IOM of Trieste for experimental assistance in the fabrication of suspended SLG and FIB analysis, and N. Secomandi and R. Rauti for assistance in imaging. We thank A. Laio, G. Scoles, A. Nistri and B. Cortés-Llanos for discussion. This paper is based on work supported by the European Union Seventh Framework Program under grant agreement no. 696656 Graphene Flagship and no. 720270 Human Brain Project Flagship, and by the Flanders Research Foundation (grant no. G0F1517N). M.P., as the recipient of the AXA Chair, is grateful to the AXA Research Fund for financial support. M.P. was also supported by the Spanish Ministry of Economy and Competitiveness MINECO (project CTQ2016-76721-R), by the University of Trieste and by Diputación Foral de Gipuzkoa program Red (101).

Author information

Author notes

    • Alessia Matruglio

    Present address: CERIC-ERIC (Central European Research Infrastructure Consortium), Trieste, Italy

  1. These authors contributed equally: Niccolò Paolo Pampaloni, Martin Lottner


  1. International School for Advanced Studies (SISSA), Trieste, Italy

    • Niccolò Paolo Pampaloni
    • , Laura Ballerini
    •  & Denis Scaini
  2. Walter Schottky Institut and Physik-Department, Technische Universität München, Garching, Germany

    • Martin Lottner
  3. Molecular, Cellular, and Network Excitability, Department of Biomedical Sciences, Universiteit Antwerp, Antwerp, Belgium

    • Michele Giugliano
  4. Department of Computer Science, University of Sheffield, Sheffield, UK

    • Michele Giugliano
  5. Lab of Neural Microcircuitry, Brain Mind Institute, EPFL, Lausanne, Switzerland

    • Michele Giugliano
  6. CNR-IOM—Istituto Officina dei Materiali, Trieste, Italy

    • Alessia Matruglio
  7. Elettra Sincrotrone Trieste S.C.p.A., Trieste, Italy

    • Francesco D’Amico
    •  & Denis Scaini
  8. Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy

    • Maurizio Prato
  9. Nanobiotechnology Laboratory, CIC biomaGUNE, San Sebastiàn, Spain

    • Maurizio Prato
  10. Ikerbasque, Basque Foundation for Science, Bilbao, Spain

    • Maurizio Prato
  11. Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and The Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, Spain

    • Josè Antonio Garrido
  12. ICREA3, Barcelona, Spain

    • Josè Antonio Garrido


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N.P.P. performed electrophysiological experiments, imaging, immunochemistry, confocal microscopy and all the related analysis. M.L. fabricated supported SLG and MLG and performed all material characterization. M.G. performed mathematical simulations and analysis and contributed to the writing of the manuscript; A.M. fabricated suspended SLG and gold-plated samples. F.D.A. and A.M. performed Raman experiments and data analysis on SLG and MLG in wet and dried conditions. M.P., D.S. and L.B. conceived the study. D.S., L.B. and J.A.G. designed the experimental strategy, interpreted the results and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Josè Antonio Garrido or Laura Ballerini or Denis Scaini.

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