Summary
Little is known about how individual cells sense the macroscopic geometry of their tissue environment. Here we explore whether long-range electrical signaling can convey information on tissue geometry to individual cells. First, we studied an engineered electrically excitable cell line. Cells grown in patterned islands of different shapes showed remarkably diverse firing patterns under otherwise identical conditions, including regular spiking, period-doubling alternans, and arrhythmic firing. A Hodgkin-Huxley numerical model quantitatively reproduced these effects, showing how the macroscopic geometry affected the single-cell electrophysiology via the influence of gap junction-mediated electrical coupling. Qualitatively similar geometry dependent dynamics were observed in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. The cardiac results urge caution in translating observations of arrhythmia in vitro to predictions in vivo where the tissue geometry is very different. We study how to extrapolate electrophysiological measurements between tissues with different geometries and different gap junction couplings.
Spiral wave patterns observed in models of cardiac arrhythmias and chemical oscillations develop alternans and stationary line defects, which can both be thought of as period-doubling instabilities. These instabilities are observed on bounded domains, and may be caused by the spiral core, far-field asymptotics, or boundary conditions. Here, we introduce a methodology to disentangle the impacts of each region on the instabilities by analyzing spectral properties of spiral waves and boundary sinks on bounded domains with appropriate boundary conditions. We apply our techniques to spirals formed in reaction-diffusion systems to investigate how and why alternans and line defects develop. Our results indicate that the mechanisms driving these instabilities are quite different; alternans are driven by the spiral core, whereas line defects appear from boundary effects. Moreover, we find that the shape of the alternans eigenfunction is due to the interaction of a point eigenvalue with curves of continuous spectra.
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