A device for rapid and quantitative measurement of cardiac myocyte contractility.
A device for rapid and quantitative measurement of cardiac myocyte contractility.
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DOI：
10.1063/1.4915500
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
A. Gaitas;R. Malhotra;Tao Li;T. Herron;J. Jalife
中科院分区：
文献类型：
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作者：
A. Gaitas;R. Malhotra;Tao Li;T. Herron;J. Jalife
心肌收缩力是心脏功能的标志，是健康或患病心肌的预测指标。尽管在过去的二十年中取得了进步，但心血管科学家可用的技术和工具在准确可靠地测量心肌细胞收缩的幅度和频率方面的实用性有限。在过去，等长力测量需要将分离的和透化的心肌细胞繁琐地附着到力传感器上，然后在次最大和最大Ca（2+）激活条件下测量肌节长度。这些技术具有劳动密集型和昂贵的固有缺点。我们已经设计了一个微机械悬臂梁传感器，嵌入式偏转传感元件，在初步实验中，已被证明可以可靠地实时测量心脏细胞收缩。在这里，我们描述了这种新的生物工程工具，适用于心血管研究领域，以有效和可靠地定量测量心脏细胞收缩力。我们测量了原代新生大鼠心脏心肌细胞单层的收缩性，其表现出3 Hz的搏动频率，以及人胚胎干细胞衍生的心肌细胞的收缩频率约为1 Hz。我们还使用了β-肾上腺素能激动剂异丙肾上腺素（100 nmol l（-1）），并观察到我们的悬臂梁在检测单层变时性和变力性反应的细微变化方面表现出高灵敏度。这份报告描述了我们的微型设备在基础心血管研究以及小分子药物发现中的效用，以监测心脏细胞收缩。
Cardiac contractility is the hallmark of cardiac function and is a predictor of healthy or diseased cardiac muscle. Despite advancements over the last two decades, the techniques and tools available to cardiovascular scientists are limited in their utility to accurately and reliably measure the amplitude and frequency of cardiomyocyte contractions. Isometric force measurements in the past have entailed cumbersome attachment of isolated and permeabilized cardiomyocytes to a force transducer followed by measurements of sarcomere lengths under conditions of submaximal and maximal Ca(2+) activation. These techniques have the inherent disadvantages of being labor intensive and costly. We have engineered a micro-machined cantilever sensor with an embedded deflection-sensing element that, in preliminary experiments, has demonstrated to reliably measure cardiac cell contractions in real-time. Here, we describe this new bioengineering tool with applicability in the cardiovascular research field to effectively and reliably measure cardiac cell contractility in a quantitative manner. We measured contractility in both primary neonatal rat heart cardiomyocyte monolayers that demonstrated a beat frequency of 3 Hz as well as human embryonic stem cell-derived cardiomyocytes with a contractile frequency of about 1 Hz. We also employed the β-adrenergic agonist isoproterenol (100 nmol l(-1)) and observed that our cantilever demonstrated high sensitivity in detecting subtle changes in both chronotropic and inotropic responses of monolayers. This report describes the utility of our micro-device in both basic cardiovascular research as well as in small molecule drug discovery to monitor cardiac cell contractions.