Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
The Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Int J Mol Sci. 2023 Aug 30;24(17):13416. doi: 10.3390/ijms241713416.
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in cardiac disease modeling, drug screening, and regenerative medicine. Furthermore, patient-specific iPSC-CMS can be tested for personalized medicine. To provide a deeper understanding of the contractile force dynamics of iPSC-CMs, we employed Atomic Force Microscopy (AFM) as an advanced detection tool to distinguish the characteristics of force dynamics at a single cell level. We measured normal (vertical) and lateral (axial) force at different pacing frequencies. We found a significant correlation between normal and lateral force. We also observed a significant force-frequency relationship for both types of forces. This work represents the first demonstration of the correlation of normal and lateral force from individual iPSC-CMs. The identification of this correlation is relevant because it validates the comparison across systems and models that can only account for either normal or lateral force. These findings enhance our understanding of iPSC-CM properties, thereby paving the way for the development of therapeutic strategies in cardiovascular medicine.
诱导多能干细胞衍生的心肌细胞（iPSC-CMs）在心脏疾病建模、药物筛选和再生医学方面具有巨大的潜力。此外，还可以对患者特异性的 iPSC-CMS 进行个性化药物测试。为了更深入地了解 iPSC-CMs 的收缩力动力学特性，我们采用原子力显微镜（AFM）作为一种先进的检测工具，以区分单细胞水平的力动力学特征。我们测量了不同起搏频率下的正常（垂直）和横向（轴向）力。我们发现正常力和横向力之间存在显著的相关性。我们还观察到这两种力都具有显著的力-频率关系。这项工作首次证明了来自单个 iPSC-CMs 的正常力和横向力之间的相关性。这种相关性的确定具有重要意义，因为它验证了可以仅考虑正常力或横向力的跨系统和模型之间的比较。这些发现增强了我们对 iPSC-CM 特性的理解，从而为心血管医学中的治疗策略的发展铺平了道路。
