NanoMEA: A Tool for High-Throughput, Electrophysiological Phenotyping of Patterned Excitable Cells

Matrix nanotopographical cues are known to regulate the structure and function of somatic cells derived from human pluripotent stem cell (hPSC) sources. High-throughput electrophysiological analysis of excitable cells derived from hPSCs is possible via multielectrode arrays (MEAs) but conventional M...

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Published in:	Nano letters 2020-03, Vol.20 (3), p.1561-1570
Main Authors:	Smith, Alec S. T, Choi, Eunpyo, Gray, Kevin, Macadangdang, Jesse, Ahn, Eun Hyun, Clark, Elisa C, Laflamme, Michael A, Wu, Joseph C, Murry, Charles E, Tung, Leslie, Kim, Deok-Ho
Format:	Article
Language:	eng
Subjects:	Cell Differentiation Electrodes Electrophysiological Phenomena Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Neurons - cytology Neurons - metabolism
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Summary:	Matrix nanotopographical cues are known to regulate the structure and function of somatic cells derived from human pluripotent stem cell (hPSC) sources. High-throughput electrophysiological analysis of excitable cells derived from hPSCs is possible via multielectrode arrays (MEAs) but conventional MEA platforms use flat substrates and do not reproduce physiologically relevant tissue-specific architecture. To address this issue, we developed a high-throughput nanotopographically patterned multielectrode array (nanoMEA) by integrating conductive, ion-permeable, nanotopographic patterns with 48-well MEA plates, and investigated the effect of substrate-mediated cytoskeletal organization on hPSC-derived cardiomyocyte and neuronal function at scale. Using our nanoMEA platform, we found patterned hPSC-derived cardiac monolayers exhibit both enhanced structural organization and greater sensitivity to treatment with calcium blocking or conduction inhibiting compounds when subjected to high-throughput dose–response studies. Similarly, hPSC-derived neurons grown on nanoMEA substrates exhibit faster migration and neurite outgrowth speeds, greater colocalization of pre- and postsynaptic markers, and enhanced cell–cell communication only revealed through examination of data sets derived from multiple technical replicates. The presented data highlight the nanoMEA as a new tool to facilitate high-throughput, electrophysiological analysis of ordered cardiac and neuronal monolayers, which can have important implications for preclinical analysis of excitable cell function.
ISSN:	1530-6984 1530-6992