Heart-on-a-Chip Model with Integrated Extra- and Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia
| Autor: | Ning Hu, Breanna M. Duffy, Akshita A. Rao, Zhaohui Huang, Lauren D. Black, Jie Ju, Olurotimi A. Bolonduro, Haitao Liu, Brian P. Timko |
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| Rok vydání: | 2020 |
| Předmět: |
Cardiac function curve
Action Potentials Bioengineering 02 engineering and technology Cell Line Mice Heart Rate Lab-On-A-Chip Devices medicine Animals Humans General Materials Science Hypoxia Bioelectronics Chemistry Cardiac electrophysiology Mechanical Engineering Electroporation Arrhythmias Cardiac Heart Equipment Design General Chemistry Hypoxia (medical) 021001 nanoscience & nanotechnology Condensed Matter Physics Electrophysiological Phenomena Electrophysiology Membrane repolarization medicine.symptom Electrophysiologic Techniques Cardiac 0210 nano-technology Neuroscience Intracellular |
| Zdroj: | Nano Letters. 20:2585-2593 |
| ISSN: | 1530-6992 1530-6984 |
| Popis: | We demonstrated a bioelectronic heart-on-a-chip model for studying the effects of acute hypoxia on cardiac function. A microfluidic channel enabled rapid modulation of medium oxygenation, which mimicked the regimes induced by a temporary coronary occlusion and reversibly activated hypoxia-related transduction pathways in HL-1 cardiac model cells. Extracellular bioelectronics provided continuous readouts demonstrating that hypoxic cells experienced an initial period of tachycardia followed by a reduction in beat rate and eventually arrhythmia. Intracellular bioelectronics consisting of Pt nanopillars temporarily entered the cytosol following electroporation, yielding action potential (AP)-like readouts. We found that APs narrowed during hypoxia, consistent with proposed mechanisms by which oxygen deficits activate ATP-dependent K+ channels that promote membrane repolarization. Significantly, both extra- and intracellular devices could be multiplexed, enabling mapping capabilities unachievable by other electrophysiological tools. Our platform represents a significant advance toward understanding electrophysiological responses to hypoxia and could be applicable to disease modeling and drug development. |
| Databáze: | OpenAIRE |
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