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

Int J Mol Sci. 2023 Aug 30;24(17):13416. doi: 10.3390/ijms241713416.

Abstract

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.

Keywords: Atomic Force Microscopy (AFM); contractile force; force dynamics; force–frequency relationship; induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs); normal and lateral force correlation; single-cell lateral force; single-cell mechanics; single-cell normal force.

MeSH terms

  • Cardiovascular Diseases* / therapy
  • Humans
  • Induced Pluripotent Stem Cells*
  • Myocytes, Cardiac
  • Precision Medicine
  • Single-Cell Analysis