Enhancement of cardiac contractility using gold-coated SU-8 cantilevers and their application to drug-induced cardiac toxicity tests,Analyst

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Enhancement of cardiac contractility using gold-coated SU-8 cantilevers and their application to drug-induced cardiac toxicity tests
Analyst ( IF 3.6 ) Pub Date : 2021-10-04 , DOI: 10.1039/d1an01337h
Jongyun Kim ₁ , Arunkumar Shanmugasundaram ₂ , Dong-Weon Lee _{2,

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Affiliation

Herein, we propose an array of gold (Au)-coated SU-8 cantilevers with microgrooves for improved maturation of cardiomyocytes and describe its applications to drug-induced cardiac toxicity tests. Firstly, we evaluated the effect of cell culture substrates such as polydimethylsiloxane (PDMS), polyimide (PI), and SU-8 on the cardiomyocyte's maturation. Among these, the SU-8 with microgroove structures exhibits improved cardiomyocyte maturation. Further, thin layers of graphene and Au are coated on SU-8 substrates and the effects of these materials on cardiomyocyte maturation are evaluated by analyzing the expression of proteins such as alpha-actinin, Connexin 43 (Cx43), and Vinculin. While both conductive materials enhanced protein expression when compared to bare SU-8, the Au-coated SU-8 substrates demonstrated superior cardiomyocyte maturation. The cantilever structure is constructed using microgroove patterned SU-8 with and without an Au coating. The Au-coated SU-8 cantilever showed maximum displacement of 17.6 ± 0.3 μm on day 21 compared to bare SU-8 (14.2 ± 0.4 μm) owing to improved cardiomyocytes maturation. Verapamil and quinidine are used to characterize drug-induced changes in the contraction characteristics of cardiomyocytes on bare and Au-coated SU-8 cantilevers. The relative contraction forces and beat rates changed according to the calcium and sodium channel related drugs. Matured cardiomyocytes are less influenced by the drugs compared to immature cardiomyocytes and showed reliable IC₅₀ values. These results indicate that the proposed Au-coated SU-8 cantilever array could help improve the accuracy of toxicity screening results by allowing for the use of cardiomyocytes that have been matured on the drug screening platform.

中文翻译：

使用镀金 SU-8 悬臂增强心脏收缩力及其在药物诱导的心脏毒性试验中的应用

在此，我们提出了一系列带有微槽的金 (Au) 涂层 SU-8 悬臂，以提高心肌细胞的成熟度，并描述了其在药物诱导的心脏毒性测试中的应用。首先，我们评估了细胞培养基质如聚二甲基硅氧烷 (PDMS)、聚酰亚胺 (PI) 和 SU-8 对心肌细胞成熟的影响。其中，具有微槽结构的 SU-8 表现出改善的心肌细胞成熟度。此外，石墨烯和金的薄层涂在 SU-8 基底上，并通过分析 α-肌动蛋白、连接蛋白 43 (Cx43) 和纽蛋白等蛋白质的表达来评估这些材料对心肌细胞成熟的影响。虽然与裸露的 SU-8 相比，这两种导电材料都增强了蛋白质表达，但涂有金的 SU-8 基材表现出优异的心肌细胞成熟度。悬臂结构是使用带有和不带有 Au 涂层的微槽图案 SU-8 构建的。由于改善了心肌细胞的成熟，与裸露的 SU-8 (14.2 ± 0.4 μm) 相比，Au 涂层的 SU-8 悬臂在第 21 天显示出 17.6 ± 0.3 μm 的最大位移。维拉帕米和奎尼丁用于表征药物引起的裸露和镀金 SU-8 悬臂上心肌细胞收缩特性的变化。相对收缩力和搏动率根据钙和钠通道相关药物而变化。与未成熟心肌细胞相比，成熟心肌细胞受药物影响较小，并显示出可靠的 IC 由于心肌细胞成熟度提高，第 21 天为 3 μm，而裸 SU-8 (14.2 ± 0.4 μm) 为 3 μm。维拉帕米和奎尼丁用于表征药物引起的裸露和镀金 SU-8 悬臂上心肌细胞收缩特性的变化。相对收缩力和搏动率根据钙和钠通道相关药物而变化。与未成熟心肌细胞相比，成熟心肌细胞受药物影响较小，并显示出可靠的 IC 由于心肌细胞成熟度提高，第 21 天为 3 μm，而裸 SU-8 (14.2 ± 0.4 μm) 为 3 μm。维拉帕米和奎尼丁用于表征药物引起的裸露和镀金 SU-8 悬臂上心肌细胞收缩特性的变化。相对收缩力和搏动率根据钙和钠通道相关药物而变化。与未成熟心肌细胞相比，成熟心肌细胞受药物影响较小，并显示出可靠的 IC_{50 个}值。这些结果表明，所提出的镀金 SU-8 悬臂阵列可以通过允许使用在药物筛选平台上成熟的心肌细胞来帮助提高毒性筛选结果的准确性。

更新日期：2021-10-13

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