Abstract
Power laws are of interest to several scientific disciplines because they can provide important information about the underlying dynamics (e.g. scale invariance and self-similarity) of a given system. Because power laws are of increasing interest to the cardiac sciences as potential indicators of cardiac dysfunction, it is essential that rigorous, standardized analytical methods are employed in the evaluation of power laws. This study compares the methods currently used in the fields of condensed matter physics, geoscience, neuroscience, and cardiology in order to provide a robust analytical framework for evaluating power laws in stem cell-derived cardiomyocyte cultures. One potential power law-obeying phenomenon observed in these cultures is pacemaker translocations, or the spatial and temporal instability of the pacemaker region, in a 2D cell culture. Power law analysis of translocation data was performed using increasingly rigorous methods in order to illustrate how differences in analytical robustness can result in misleading power law interpretations. Non-robust methods concluded that pacemaker translocations adhere to a power law while robust methods convincingly demonstrated that they obey a doubly truncated power law. The results of this study highlight the importance of employing comprehensive methods during power law analysis of cardiomyocyte cultures.
Highlights
MethodsCell cultures & microelectrode array measurementsHuman ESCs were grown and differentiated in a chemically defined condition as previously described [8, 55, 56]
Recent investigations of human induced pluripotent and embryonic stem cell-derived cardiomyocytes have shone significant light on numerous factors contributing to the development of the heart [1–6]
Usage of all the human embryonic stem cell lines is approved by the UCLA Embryonic Stem Cell Research Oversight (ESCRO) Committee and the Institutional Review Boards (IRB)
Summary
Cell cultures & microelectrode array measurementsHuman ESCs were grown and differentiated in a chemically defined condition as previously described [8, 55, 56]. Differentiation efficiency is checked periodically by flow cytometry and maintained around 80–90%. Cardiomyocytes were plated, without performing any extra purification step, as twodimensional monolayers on matrigel-coated (Corning #354277), commercially available microelectrode arrays (MEAs) containing 120 integrated TiN electrodes. All electrodes were 30 μm in diameter with an interelectrode spacing of 200 μm (Multichannel Systems, Reutlingen, Germany). The cell cultures were given a minimum of 24 hours to ensure the cardiomyocytes were well-attached to each MEA. Local field potentials at each electrode were recorded over an average period of 19.5 minutes, up to twice daily, with a sampling rate of 1 KHz using the MEA2100-HS120 system (Multichannel Systems, Reutlingen, Germany). The full data acquisition yielded 30 MEA recordings across 3 distinct cardiomyocyte cell cultures
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