1. NanoMEA: A Tool for High-Throughput, Electrophysiological Phenotyping of Patterned Excitable Cells.
- Author
-
Smith AST, Choi E, Gray K, Macadangdang J, Ahn EH, Clark EC, Laflamme MA, Wu JC, Murry CE, Tung L, and Kim DH
- Subjects
- Electrodes, Humans, Induced Pluripotent Stem Cells cytology, Myocytes, Cardiac cytology, Neurons cytology, Cell Differentiation, Electrophysiological Phenomena, Induced Pluripotent Stem Cells metabolism, Myocytes, Cardiac metabolism, Neurons metabolism
- 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.
- Published
- 2020
- Full Text
- View/download PDF