Cardiac cells in the heart and neurons in the brain communicate by electrical signals, and these messages of communication travel fast from cell to cell as “excitation waves.”

For heart patients there are currently two options to keep these waves in check: electrical devices (pacemakers or defibrillators) or drugs (e.g., beta blockers). However, these methods are relatively crude: they can stop or start waves but cannot provide fine control over the wave speed and direction.

Gil Bub, from Oxford University explained: ‘When there is scar tissue in the heart or fibrosis, this can cause part of the wave to slow down. That can cause re-entrant waves which spiral back around the tissue, causing the heart to beat much too quickly, which can be fatal. If we can control these spirals, we could prevent that.

The optogenetics solution

The solution the researchers found was optogenetics, which uses genetic modification to alter cells so that they can be activated by light. Until now, it has mainly been used to activate individual cells or to trigger excitation waves in tissue, especially in neuroscience research. “We wanted to use it to very precisely control the activity of millions of cells,” said Bub.

A light-activated protein called channelrhodopsin was delivered to heart cells using gene therapy techniques so that they could be controlled by light. Then, using a computer-controlled light projector, the team was able to control the speed of the cardiac waves, their direction and even the orientation of spirals in real time — something that never been shown for waves in a living system before.

In the short term, the ability to provide fine control means that researchers are able to carry out experiments at a level of detail previously only available using computer models. They can now compare those models to experiments with real cells, potentially improving our understanding of how the heart works. The research can also be applied to the physics of such waves in other processes. In the long run, it might be possible to develop precise treatments for heart conditions.

“Precise control of the direction, speed and shape of such excitation waves would mean unprecedented direct control of organ-level function, in the heart or brain, without having to focus on manipulating each cell individually,” said Stony Brook University scientist Emilia Entcheva.

The team stresses that there are significant hurdles before this could offer new treatments; a key issue is being able to alter the heart to be light-sensitized and being able to get the light to desired locations. However, as gene therapy moves into the clinic and with miniaturization of optical devices, use of this all-optical technology may become possible.

In the meantime, the research enables scientists to look into the physics behind many biological processes, including those in our own brains and hearts.

University of Oxford | Controlling heart tissue with light

Abstract of Optical control of excitation waves in cardiac tissue

In nature, macroscopic excitation waves 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 states. 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 reaction. 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.