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Bioelectrical domain walls in homogeneous tissues

Nature Physics volume 16, pages 357–364 (2020)Cite this article

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Abstract

Electrical signalling in biology is typically associated with action potentials—transient spikes in membrane voltage that return to baseline. Hodgkin–Huxley and related conductance-based models of electrophysiology belong to a more general class of reaction–diffusion equations that could, in principle, support the spontaneous emergence of patterns of membrane voltage that are stable in time but structured in space. Here, we show theoretically and experimentally that homogeneous or nearly homogeneous tissues can undergo spontaneous spatial symmetry breaking through a purely electrophysiological mechanism, leading to the formation of domains with different resting potentials separated by stable bioelectrical domain walls. Transitions from one resting potential to another can occur through long-range migration of these domain walls. We map bioelectrical domain wall motion using all-optical electrophysiology in an engineered cell line and in human induced pluripotent stem cell (iPSC)-derived myoblasts. Bioelectrical domain wall migration may occur during embryonic development and during physiological signalling processes in polarized tissues. These results demonstrate that nominally homogeneous tissues can undergo spontaneous bioelectrical spatial symmetry breaking.

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Fig. 1: Biochemical and bioelectrical spontaneous pattern formation.
Fig. 2: Electrophysiological bistability in an engineered cell line.
Fig. 3: Bioelectric domain walls in an engineered cell line.
Fig. 4: Bioelectric domain wall propagation in stem cell-derived myocytes.

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Data availability

The plots of fluorescent voltage recordings in Figs. 2–4 are available as Source Data. All other data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

Code availability

Custom-written code used for data analysis is available from the authors upon request.

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Acknowledgements

We thank U. Böhm, A. Klaeger, J. Mathews and M. Levin for helpful discussions. We thank E. Miller for help providing the BeRST1 dye. This work was supported by the Allen Discovery Center at Tufts University, the Vannevar Bush Fellowship Foundation and the Howard Hughes Medical Institute. H.M.M. was supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program. G.O. was supported by the Howard Hughes Medical Institute Gilliam Fellowship.

Author information

Author notes

  1. Haitan Xu

    Present address: State Key Laboratory for Mesoscopic Physics and Frontiers Science Center for Nano-optoelectronics, School of Physics, Peking University, Beijing, China

Authors and Affiliations

  1. Department of Physics, Harvard University, Cambridge, MA, USA

    Harold M. McNamara & Adam E. Cohen

  2. Harvard–MIT Division of Health Sciences and Technology, Cambridge, MA, USA

    Harold M. McNamara

  3. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA

    Rajath Salegame, Haitan Xu, Shahinoor Begum & Adam E. Cohen

  4. Department of Genetics, Harvard Medical School, Cambridge, MA, USA

    Ziad Al Tanoury & Olivier Pourquie

  5. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Ziad Al Tanoury & Olivier Pourquie

  6. Department of Chemistry, University of California Berkeley, Berkeley, CA, USA

    Gloria Ortiz

  7. Howard Hughes Medical Institute, Cambridge, MA, USA

    Adam E. Cohen

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Contributions

H.M.M. and A.E.C. conceived and designed the study. H.M.M. conducted experiments and analysed results, with assistance from R.S., H.X. and S.B. H.M.M. designed and simulated numerical models of electrically bistable cells. Z.A.T. and O.P. provided hiPSC-derived myoblasts for myocyte differentiation and characterized these cells via immunocytochemistry and RNA-seq. G.O. provided BeRST1 dye reagent. H.M.M. and A.E.C. wrote the manuscript, with input from Z.A.T. and O.P. A.E.C. and O.P. oversaw the research.

Corresponding author

Correspondence to Adam E. Cohen.

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The authors declare no competing interests.

Additional information

Peer review information Nature Physics thanks Salvador Mafe, Min Zhao and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–9, Tables 1 and 2, and video captions 1–6.

Supplementary Video 1

Simulation of nucleation and growth of bioelectrical domains in homogeneous tissue.

Supplementary Video 2

Nucleation and growth of bioelectrical domains in a confluent culture of bi-HEK cells, example 1.

Supplementary Video 3

Nucleation and growth of bioelectrical domains in a confluent culture of bi-HEK cells, example 2.

Supplementary Video 4

Switching of discrete bistable bioelectrical domains in disordered culture of bi-HEK cells.

Supplementary Video 5

Simulation of switching of discrete bistable bioelectrical domains in disordered tissue.

Supplementary Video 6

Depolarization via domain wall propagation in a confluent culture of human iPSC-derived myocytes.

Source data

Source Data Fig. 2

Fluorescence vs. time for Fig. 2e

Source Data Fig. 3

Fluorescence vs. time for Fig. 3f

Source Data Fig. 4

Fluorescence vs. time for Fig. 4c,g

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McNamara, H.M., Salegame, R., Tanoury, Z.A. et al. Bioelectrical domain walls in homogeneous tissues. Nat. Phys. 16, 357–364 (2020). https://doi.org/10.1038/s41567-019-0765-4

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