Single-Cell Analysis of Contractile Forces in iPSC-Derived Cardiomyocytes: Paving the Way for Precision Medicine in Cardiovascular Disease.

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潜力。此外，可针对患者特异性的iPSC - CMs进行个性化医疗测试。为了更深入地了解iPSC - CMs的收缩力动态，我们采用原子力显微镜（AFM）作为一种先进的检测工具，在单细胞水平上区分力动态的特征。我们测量了不同起搏频率下的法向（垂直）力和侧向（轴向）力。我们发现法向力和侧向力之间存在显著的相关性。我们还观察到两种力都存在显著的力 - 频率关系。这项工作首次展示了单个iPSC - CMs的法向力和侧向力的相关性。这种相关性的确定是有意义的，因为它验证了只能考虑法向力或侧向力的不同系统和模型之间的比较。这些发现增进了我们对iPSC - CM特性的理解，从而为心血管医学治疗策略的发展铺平了道路。