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Optical control of excitation waves in cardiac tissue

Abstract

In nature, macroscopic excitation waves1,2 are found in a diverse range of settings including chemical reactions, metal rust, yeast, amoeba and the heart and brain. In the case of living biological tissue, the spatiotemporal patterns formed by these excitation waves are different in healthy and diseased states2,3. Current electrical and pharmacological methods for wave modulation lack the spatiotemporal precision needed to control these patterns. Optical methods have the potential to overcome these limitations, but to date have only been demonstrated in simple systems, such as the Belousov–Zhabotinsky chemical reaction4. Here, we combine dye-free optical imaging with optogenetic actuation to achieve dynamic control of cardiac excitation waves. Illumination with patterned light is demonstrated to optically control the direction, speed and spiral chirality of such waves in cardiac tissue. This all-optical approach offers a new experimental platform for the study and control of pattern formation in complex biological excitable systems.

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Figure 1: All-optical system for control of wave dynamics in biological media.
Figure 2: Optical control of cardiac wave direction.
Figure 3: Optical control of cardiac wave conduction velocity.
Figure 4: Optical control of spiral wave chirality in cardiac monolayer.

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References

  1. Krinsky, V. I. Self-Organization: Autowaves and Structures Far From Equilibrium (Springer, 1984).

    Book  Google Scholar 

  2. Winfree, A. T. The Geometry of Biological Time Vol. 12 (Springer Science & Business Media, 2001).

    Book  Google Scholar 

  3. Davidenko, J., Pertsov, A., Salomonsz, R., Baxter, W. & Jalife, J. Stationary and drifting spiral waves of excitation in isolated cardiac muscle. Nature 355, 349–351 (1992).

    Article  ADS  Google Scholar 

  4. Steinbock, O. & MĂĽller, S. C. Light-controlled anchoring of meandering spiral waves. Phys. Rev. E 47, 1506 (1993).

    Article  ADS  Google Scholar 

  5. Mines, G. On circulating excitations in heart muscles and their possible relation to tachycardia and fibrillation. Trans. R. Soc. Canada 43–55 (1914).

  6. Garrey, W. E. The nature of fibrillary contraction of the heart: its relation to tissue mass and form. Am. J. Physiol. 33, 397–414 (1914).

    Article  Google Scholar 

  7. Shajahan, T. K., Nayak, A. R. & Pandit, R. Spiral-wave turbulence and its control in the presence of inhomogeneities in four mathematical models of cardiac tissue. PLoS ONE 4, e4738 (2009).

    Article  ADS  Google Scholar 

  8. Miura, K. & Siegert, F. Light affects cAMP signaling and cell movement activity in Dictyostelium discoideum. Proc. Natl Acad. Sci. USA 97, 2111–2116 (2000).

    Article  ADS  Google Scholar 

  9. Jenkins, M. W. et al. Optical pacing of the embryonic heart. Nature Photon. 4, 623–626 (2010).

    Article  ADS  Google Scholar 

  10. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005).

    Article  Google Scholar 

  11. Nagel, G. et al. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc. Natl Acad. Sci. USA 100, 13940–13945 (2003).

    Article  ADS  Google Scholar 

  12. Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M. & Deisseroth, K. Optogenetics in neural systems. Neuron 71, 9–34 (2011).

    Article  Google Scholar 

  13. Lima, S. Q. & Miesenböck, G. Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121, 141–152 (2005).

    Article  Google Scholar 

  14. Ambrosi, C. M., Klimas, A., Yu, J. & Entcheva, E. Cardiac applications of optogenetics. Prog. Biophys. Mol. Biol. 115, 294–304 (2014).

    Article  Google Scholar 

  15. Bruegmann, T. et al. Optogenetic control of heart muscle in vitro and in vivo. Nature Methods 7, 897–900 (2010).

    Article  Google Scholar 

  16. Jia, Z. et al. Stimulating cardiac muscle by light cardiac optogenetics by cell delivery. Circ. Arrhythmia Electrophysiol. 4, 753–760 (2011).

    Article  Google Scholar 

  17. Arrenberg, A. B., Stainier, D. Y. R., Baier, H. & Huisken, J. Optogenetic control of cardiac function. Science 330, 971–974 (2010).

    Article  ADS  Google Scholar 

  18. Bingen, B. O. et al. Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes. Cardiovasc. Res. 104, 194–205 (2014).

    Article  Google Scholar 

  19. Hochbaum, D. R. et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nature Methods 11, 825–833 (2014).

    Article  Google Scholar 

  20. Bub, G., Glass, L., Publicover, N. G. & Shrier, A. Bursting calcium rotors in cultured cardiac myocyte monolayers. Proc. Natl Acad. Sci. USA 95, 10283–10287 (1998).

    Article  ADS  Google Scholar 

  21. Tung, L. & Zhang, Y. Optical imaging of arrhythmias in tissue culture. J. Electrocardiol. 39, S2–S6 (2006).

    Article  Google Scholar 

  22. Ambrosi, C. M. & Entcheva, E. Optogenetic control of cardiomyocytes via viral delivery. Methods Mol. Biol. 1181, 215–228 (2014).

    Article  Google Scholar 

  23. Hwang, S.-M., Yea, K.-H. & Lee, K. J. Regular and alternant spiral waves of contractile motion on rat ventricle cell cultures. Phys. Rev. Lett. 92, 198103 (2004).

    Article  ADS  Google Scholar 

  24. Hwang, S.-M., Kim, T. Y. & Lee, K. J. Complex-periodic spiral waves in confluent cardiac cell cultures induced by localized inhomogeneities. Proc. Natl Acad. Sci. USA 102, 10363–10368 (2005).

    Article  ADS  Google Scholar 

  25. Wiener, N. & Rosenblueth, A. The mathematical formulation of the problem of conduction of impulses in a network of connected excitable elements, specifically in cardiac muscle. Arch. del Inst. Cardiol. México 16, 205–265 (1946).

    MathSciNet  MATH  Google Scholar 

  26. Jia, Z., Bien, H., Shiferaw, Y. & Entcheva, E. Cardiac cellular coupling and the spread of early instabilities in intracellular Ca2+. Biophys. J. 102, 1294–1302 (2012).

    Article  ADS  Google Scholar 

  27. Ambrosi, C. M., Williams, J. C. & Entcheva, E. Optogenetic modulation of pacemaking, arrhythmia generation, and inhibition with sustained (non-pulsed) light. Circulation 130, A19856 (2014).

    Google Scholar 

  28. Quail, T., Shrier, A. & Glass, L. Spatial symmetry breaking determines spiral wave chirality. Phys. Rev. Lett. 113, 158101 (2014).

    Article  ADS  Google Scholar 

  29. Li, B.-W., Cai, M.-C., Zhang, H., Panfilov, A. V. & Dierckx, H. Chiral selection and frequency response of spiral waves in reaction–diffusion systems under a chiral electric field. J. Chem. Phys. 140, 184901 (2014).

    Article  ADS  Google Scholar 

  30. Bub, G., Shrier, A. & Glass, L. Spiral wave generation in heterogeneous excitable media. Phys. Rev. Lett. 88, 058101 (2002).

    Article  ADS  Google Scholar 

  31. Bub, G., Shrier, A. & Glass, L. Global organization of dynamics in oscillatory heterogeneous excitable media. Phys. Rev. Lett. 94, 028105 (2005).

    Article  ADS  Google Scholar 

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Acknowledgements

The authors thank T. Wilson, H. Bien and S. Aslam for discussions and technical assistance, and E. Mann for use of the DMD projector (Royal Society Grant RG110135). G.B. acknowledges support from the BHF Centre of Research Excellence, Oxford (RE/08/004). R.A.B.B. holds an EPSRC Developing Leaders Grant, a Goodger award, a Winston Churchill Fellowship and Paul Nurse Junior Research Fellowship (Linacre College, Oxford). J.T. acknowledges support from the Bakala Foundation. This work was supported by MR/K015877/1 (G.B.), NIH R01 HL111649 and NSF-Biophotonics grant 1511353 (E.E.), as well as a NYSTEM grant C026716 to the Stony Brook Stem Cell Centre.

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Contributions

G.B. and E.E. initiated the project and provided guidance. R.A.B.B. and G.B. performed the experiments. G.B. wrote the software to collect and analyse the data. C.M.A. and E.E. developed and provided biological materials and guidance on the optogenetic manipulations. R.A.B.B., A.C., J.T. and A.K. helped with data interpretation and figure preparation. G.B. and E.E. wrote the manuscript with contributions from all authors. All authors were involved in analysis of the results and revision of the manuscript.

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Correspondence to Gil Bub.

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The authors declare no competing financial interests.

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Burton, R., Klimas, A., Ambrosi, C. et al. Optical control of excitation waves in cardiac tissue. Nature Photon 9, 813–816 (2015). https://doi.org/10.1038/nphoton.2015.196

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