Geometry-dependent instabilities in electrically excitable tissues

Abstract

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 influence electrical dynamics of individual cells. First, we studied an engineered electrically excitable cell line where all voltage-gated channels were known. Cells grown in patterned islands of different shapes showed remarkably diverse firing patterns, including regular spiking, period-doubling alternans, and arrhythmic firing. A spatially resolved Hodgkin-Huxley numerical model quantitatively reproduced these effects, showing how the macroscopic geometry affected the single-cell electrophysiology via 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. These findings establish that tissue geometry is a fundamental determinant of dynamical stability in excitable cells.

Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine

“…Bioelectronic devices presage the development of strategies to both monitor and guide regeneration, repair, and immune response modulation via knowledge of the bioelectronic code. To achieve the guided self-assembly needed for patterning in vivo or in bioengineering and synthetic morphology contexts (McNamara et al, 2016(McNamara et al, , 2018, closed-loop control would be desirable using strategies from biological control and machine learning that have been proposed to converge synthetic biology with bioelectronics (Selberg et al, 2018). Integration with optogenetic and microfluidic platforms is essential, as these are already beginning to interrogate cellular perception and decision-making mechanisms (Bugaj et al, 2017;Perkins et al, 2019).…”