Ultrasoft electronics to monitor dynamically pulsing cardiomyocytes

Abstract

In biointegrated electronics, the facile control of mechanical properties such as softness and stretchability in electronic devices is necessary to minimize the perturbation of motions inherent in biological systems1,2,3,4,5. For in vitro studies, multielectrode-embedded dishes6,7,8 and other rigid devices9,10,11,12 have been widely used. Soft or flexible electronics on plastic or elastomeric substrates13,14,15 offer promising new advantages such as decreasing physical stress16,17,18 and/or applying mechanical stimuli19,20. Recently, owing to the introduction of macroporous plastic substrates with nanofibre scaffolds21,22, three-dimensional electrophysiological mapping of cardiomyocytes has been demonstrated. However, quantitatively monitoring cells that exhibit significant dynamical motions via electric probes over a long period without affecting their natural motion remains a challenge. Here, we present ultrasoft electronics with nanomeshes that monitor the field potential of human induced pluripotent stem cell-derived cardiomyocytes on a hydrogel, while enabling them to move dynamically without interference. Owing to the extraordinary softness of the nanomeshes, nanomesh-attached cardiomyocytes exhibit contraction and relaxation motions comparable to that of cardiomyocytes without attached nanomeshes. Our multilayered nanomesh devices maintain reliable operations in a liquid environment, enabling the recording of field potentials of the cardiomyocytes over a period of 96 h without significant degradation of the nanomesh devices or damage of the cardiomyocytes.

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Fig. 1: Nanomesh device to monitor dynamically pulsing cardiomyocytes differentiated from hiPSCs.
Fig. 2: Stretchability of the nanomesh devices.
Fig. 3: Movement observation of nanosubstrate-attached cardiomyocyte sheets.
Fig. 4: Electrophysiological monitoring of cardiomyocytes on a fibrin hydrogel using nanomesh sensors.

Data availability

All data supporting the findings of this study are either included within the paper or available from the corresponding author upon request.

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Acknowledgements

This work was supported by JSPS KAKENHI (grant number 17H06149). The authors thank S. Lee, W. Lee and D. Ordinario for technical support and discussions.

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Affiliations

Authors

Contributions

S.L., D.K. and M.M. fabricated the nanomesh devices. D.S., K.M. and T. Shimuzu fabricated the hiPSC-derived cardiomyocytes. S.L., D.K., H.L., S.P., K.F., T.Y., M.S. and T. Someya contributed the electric and mechanical characterizations and analyses of nanomesh devices. S.L. and D.S. contributed to the strain analyses and the field potential measurements of the hiPSC-derived cardiomyocytes. S.L. and T. Someya wrote the manuscript, and T. Someya supervised this project.

Corresponding author

Correspondence to Takao Someya.

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Competing interests

There is a potential competing interest: T. Shimizu is a shareholder and a member of the scientific advisory board of CellSeed Inc. Tokyo Women’s Medical University receives a research fund from CellSeed Inc. All other authors have no competing interests.

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Supplementary Information

Supplementary Information

Supplementary Text, Supplementary References 1–7, Supplementary Figures 1–18, Supplementary Video Captions 1–6

Supplementary Video 1

Phase-contrast microscopy movie of polyurethane-only nanosubstrate attached cardiomyocytes

Supplementary Video 2

Phase-contrast microscopy movie of cardiomyocytes without attaching nanosubstrate

Supplementary Video 3

Microscopy video of polyurethane-only nanosubstrate attached cardiomyocytes without phase-contrast filter

Supplementary Video 4

Phase-contrast microscopy movie of polyurethane/100-nm-thick parylene nanosubstrate attached cardiomyocytes

Supplementary Video 5

Phase-contrast microscopy video of polyurethane/400-nm-thick parylene nanosubstrate attached cardiomyocytes

Supplementary Video 6

Microscopy video of nanomesh device attached cardiomyocytes with and without phase-contrast filter

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Lee, S., Sasaki, D., Kim, D. et al. Ultrasoft electronics to monitor dynamically pulsing cardiomyocytes. Nature Nanotech 14, 156–160 (2019). https://doi.org/10.1038/s41565-018-0331-8

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