Abstract
Complex electrical dynamics in excitable tissues occur throughout biology, but the roles of individual ion channels can be difficult to determine due to the complex nonlinear interactions in native tissue. Here, we ask whether we can engineer a tissue capable of basic information storage and processing, where all functional components are known and well understood. We develop a cell line with four transgenic components: two to enable collective propagation of electrical waves and two to enable optical perturbation and optical readout of membrane potential. We pattern the cell growth to define simple cellular ring oscillators that run stably for () and that can store data encoded in the direction of electrical circulation. Using patterned optogenetic stimulation, we probe the biophysical attributes of this synthetic excitable tissue in detail, including dispersion relations, curvature-dependent wave front propagation, electrotonic coupling, and boundary effects. We then apply the biophysical characterization to develop an optically reconfigurable bioelectric oscillator. These results demonstrate the feasibility of engineering bioelectric tissues capable of complex information processing with optical input and output.
- Received 12 April 2016
DOI:https://doi.org/10.1103/PhysRevX.6.031001
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Published by the American Physical Society
Physics Subject Headings (PhySH)
Focus
Biological Cells Form Electric Circuits
Published 1 July 2016
Cells that are electrically active and that also produce light for easy voltage monitoring could lead to new studies of heart arrhythmias and possibly bio-computing.
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Popular Summary
The electrical dynamics of the brain and heart are immensely complex and are regulated by dozens of ion channels and other macromolecular components. Here, we investigate whether it is possible to create basic aspects of function—wave propagation, oscillations, information storage, and processing—using an engineered cellular system in which all of the active components are well understood.
Starting from electrically inert human embryonic kidney cells, we use genetic engineering to imbue the cells with the ability to produce electrical spikes. When grown into a monolayer with nearest-neighbor electrical coupling, these cells support the propagation of collective electrical waves. We next introduce genetic components to trigger these waves with light and to convert the waves into a fluorescence signal, enabling optical input and output. By stimulating the cells with different patterns of light and observing the resulting wave propagation, we characterize, in detail, the biophysical properties of this synthetic bioelectrical tissue. In particular, we find that conduction velocity of the waves depends strongly on the wave front curvature but is largely independent of the stimulus frequency. We next assemble several types of cellular ring oscillators whose direction and frequency of circulation can be tuned optically. We observe that the oscillations are stable for at least 2 hours, which corresponds to roughly 10,000 cycles. Our results demonstrate that we can engineer a tissue capable of both information storage and processing.
Based on quantitative comparisons between the dynamics of our engineered cellular oscillators and real cardiac tissue, we expect that our findings will reveal insights into the factors that regulate the susceptibility of cardiac tissue to arrhythmia.