Current platforms for studying the mechanical properties of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as single cells do not measure forces directly, require numerous assumptions, and cannot study cell mechanics at different loading conditions. We present a method for directly measuring the active and passive forces generated by single-cell hPSC-CMs at different stretch levels. Utilizing this technique, single hPSC-CMs exhibited positive length-tension relationship and appropriate inotropic, klinotropic, and lusitropic changes in response to pharmacological treatments (isoproterenol and verapamil). The unique potential of the approach for drug testing and disease modeling was exemplified by doxorubicin and omecamtiv mecarbil drug studies revealing their known actions to suppress (doxorubicin) or augment (omecamtiv mecarbil at low dose) cardiomyocyte contractility, respectively. Finally, mechanistic insights were gained regarding the cellular effects of these drugs as doxorubicin treatment led to cellular mechanical alternans and high doses of omecamtiv mecarbil suppressed contractility and worsened the cellular diastolic properties.

当前研究人类多能干细胞来源的心肌细胞（hPSC-CM）力学性能的平台，因为单个细胞不能直接测量力，需要大量假设，并且不能研究不同负荷条件下的细胞力学。我们提出了一种直接测量在不同拉伸水平下单细胞hPSC-CM产生的主动和被动力的方法。利用这种技术，单个hPSC-CMs表现出正的长度-张力关系，并在药物治疗（异丙肾上腺素和维拉帕米）的反应中出现了适当的变力，溶血性和脂质变迁。阿霉素和奥美卡地美卡必尔药物研究例证了该方法在药物测试和疾病建模中的独特潜力，揭示了它们已知的抑制（阿霉素）或增强（低剂量奥美卡地美卡比）心肌细胞收缩力的已知作用。最后，关于这些药物的细胞作用获得了机械学的见解，因为阿霉素治疗可导致细胞机械性交替出现，而高剂量的omecamtiv mecarbil可抑制收缩力并恶化细胞舒张特性。