Heart-on-a-Chip Model with Integrated Extra- and Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia
Heart-on-a-Chip Model with Integrated Extra- and Intracellular Bioelectronics for Monitoring Cardiac Electrophysiology under Acute Hypoxia
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DOI：
10.1021/acs.nanolett.0c00076
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发表时间：
2020-04-08
期刊：
影响因子：
10.8
通讯作者：
Timko, Brian P.
中科院分区：
文献类型：
--
作者：
Liu, Haitao;Bolonduro, Olurotimi A.;Timko, Brian P.
我们展示了一种生物电子芯片心脏模型，用于研究急性缺氧对心脏功能的影响。微流体通道能够快速调节介质氧合，模拟 HL-1 心脏模型细胞中临时冠状动脉闭塞和可逆激活的缺氧相关转导途径诱导的状态。细胞外生物电子学提供连续读数，表明缺氧细胞经历了心动过速的初始阶段，随后是心率降低，最终出现心律失常。由 Pt 纳米柱组成的细胞内生物电子学在电穿孔后暂时进入细胞质，产生类似动作电位 (AP) 的读数。我们发现缺氧期间 AP 变窄，这与缺氧激活 ATP 依赖性 K+ 通道促进膜复极化的机制一致。值得注意的是，细胞外和细胞内设备都可以被复用，从而实现其他电生理工具无法实现的绘图功能。我们的平台代表了理解缺氧电生理反应的重大进步，可适用于疾病建模和药物开发。
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 hypoxiarelated 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.