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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Krinsky, V. I. Self-Organization: Autowaves and Structures Far From Equilibrium (Springer, 1984).
Winfree, A. T. The Geometry of Biological Time Vol. 12 (Springer Science & Business Media, 2001).
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).
Steinbock, O. & MĂĽller, S. C. Light-controlled anchoring of meandering spiral waves. Phys. Rev. E 47, 1506 (1993).
Mines, G. On circulating excitations in heart muscles and their possible relation to tachycardia and fibrillation. Trans. R. Soc. Canada 43–55 (1914).
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).
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).
Miura, K. & Siegert, F. Light affects cAMP signaling and cell movement activity in Dictyostelium discoideum. Proc. Natl Acad. Sci. USA 97, 2111–2116 (2000).
Jenkins, M. W. et al. Optical pacing of the embryonic heart. Nature Photon. 4, 623–626 (2010).
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).
Nagel, G. et al. Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc. Natl Acad. Sci. USA 100, 13940–13945 (2003).
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M. & Deisseroth, K. Optogenetics in neural systems. Neuron 71, 9–34 (2011).
Lima, S. Q. & Miesenböck, G. Remote control of behavior through genetically targeted photostimulation of neurons. Cell 121, 141–152 (2005).
Ambrosi, C. M., Klimas, A., Yu, J. & Entcheva, E. Cardiac applications of optogenetics. Prog. Biophys. Mol. Biol. 115, 294–304 (2014).
Bruegmann, T. et al. Optogenetic control of heart muscle in vitro and in vivo. Nature Methods 7, 897–900 (2010).
Jia, Z. et al. Stimulating cardiac muscle by light cardiac optogenetics by cell delivery. Circ. Arrhythmia Electrophysiol. 4, 753–760 (2011).
Arrenberg, A. B., Stainier, D. Y. R., Baier, H. & Huisken, J. Optogenetic control of cardiac function. Science 330, 971–974 (2010).
Bingen, B. O. et al. Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes. Cardiovasc. Res. 104, 194–205 (2014).
Hochbaum, D. R. et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nature Methods 11, 825–833 (2014).
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).
Tung, L. & Zhang, Y. Optical imaging of arrhythmias in tissue culture. J. Electrocardiol. 39, S2–S6 (2006).
Ambrosi, C. M. & Entcheva, E. Optogenetic control of cardiomyocytes via viral delivery. Methods Mol. Biol. 1181, 215–228 (2014).
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).
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).
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).
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).
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).
Quail, T., Shrier, A. & Glass, L. Spatial symmetry breaking determines spiral wave chirality. Phys. Rev. Lett. 113, 158101 (2014).
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).
Bub, G., Shrier, A. & Glass, L. Spiral wave generation in heterogeneous excitable media. Phys. Rev. Lett. 88, 058101 (2002).
Bub, G., Shrier, A. & Glass, L. Global organization of dynamics in oscillatory heterogeneous excitable media. Phys. Rev. Lett. 94, 028105 (2005).
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.
Author information
Authors and Affiliations
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.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary information
Supplementary information (PDF 1024 kb)
Supplementary information
Supplementary movie 1 (MP4 1817 kb)
Supplementary information
Supplementary movie 2 (MP4 13757 kb)
Supplementary information
Supplementary movie 3 (MP4 946 kb)
Supplementary information
Supplementary movie 4 (MP4 1298 kb)
Supplementary information
Supplementary movie 5 (MP4 6619 kb)
Supplementary information
Supplementary movie 6 (MP4 3260 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nphoton.2015.196
This article is cited by
-
A micro-LED array based platform for spatio-temporal optogenetic control of various cardiac models
Scientific Reports (2023)
-
In silico optical modulation of spiral wave trajectories in cardiac tissue
PflĂĽgers Archiv - European Journal of Physiology (2023)
-
Optogenetic Modulation of Arrhythmia Triggers: Proof-of-Concept from Computational Modeling
Cellular and Molecular Bioengineering (2023)
-
Millimetre-scale magnetocardiography of living rats with thoracotomy
Communications Physics (2022)
-
A one-photon endoscope for simultaneous patterned optogenetic stimulation and calcium imaging in freely behaving mice
Nature Biomedical Engineering (2022)