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University of Washington, Johns Hopkins University

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Nano Lett., Publication Date:December 17, 2019 | https://doi.org/10.1021/acs.nanolett.9b04152 NanoMEA: A Tool for High-Throughput, Electrophysiological Phenotyping of Patterned Excitable Cells

Alec S. T. Smith,^†,‡,§Eunpyo Choi,^†,∥ Kevin Gray,^†,⊥Jesse Macadangdang,^†,⊥ Eun Hyun Ahn,^§,#Elisa C. Clark,^† Michael A. Laflamme,^∇Joseph C. Wu,^○Charles E. Murry,^{†,‡,§,#,◆} Leslie Tung,^¶and Deok-Ho Kim^{*,†,‡,§,¶,□}

^†Department of Bioengineering, University of Washington, Seattle, Washington 98195, United States
^‡Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, United States
^§Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, United States
^∥ Department of Mechanical Engineering, Chonnam National University, Gwangju 61186, South Korea
^⊥NanoSurface Biomedical, Inc. Seattle, Washington 98195, United States
^# Department of Pathology, University of Washington, Seattle, Washington 98195, United States
^∇Toronto General Hospital Research Institute, McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario M5G 2C4, Canada
^○ Stanford Cardiovascular Institute, Stanford University, Stanford, California 94305, United States
^◆ Department of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, United States
^¶Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, United States
^□Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, United States

^*Corresponding Author : Deok-Ho Kim

Abstract

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.

KEYWORDS : Multielectrode arrays, nanotopography, cardiomyocyte, neuron, iPSC, electrophysiology

논문정보

형식Research article
게재일2019년 12월 (BRIC 등록일 2020-01-03)
연구진국내+국외 연구진
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