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.
Original language | English (US) |
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Pages (from-to) | 1561-1570 |
Number of pages | 10 |
Journal | Nano Letters |
Volume | 20 |
Issue number | 3 |
DOIs | |
State | Published - Mar 11 2020 |
Keywords
- Multielectrode arrays
- cardiomyocyte
- electrophysiology
- iPSC
- nanotopography
- neuron
ASJC Scopus subject areas
- Bioengineering
- General Chemistry
- General Materials Science
- Condensed Matter Physics
- Mechanical Engineering