Related Experiment Video
Updated: Dec 24, 2025
In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes
Published on: June 22, 2020
Mechanobiology Assays with Applications in Cardiomyocyte Biology and Cardiotoxicity
Cheavar A Blair1,2, Beth L Pruitt1,2,3
1Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA, 93109, USA.
Abstract:
Cardiomyocytes are the motor units that drive the contraction and relaxation of the heart. Traditionally, testing of drugs for cardiotoxic effects has relied on primary cardiomyocytes from animal models and focused on short-term, electrophysiological, and arrhythmogenic effects. However, primary cardiomyocytes present challenges arising from their limited viability in culture, and tissue from animal models suffers from a mismatch in their physiology to that of human heart muscle. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can address these challenges. They also offer the potential to study not only electrophysiological effects but also changes in cardiomyocyte contractile and mechanical function in response to cardiotoxic drugs. With growing recognition of the long-term cardiotoxic effects of some drugs on subcellular structure and function, there is increasing interest in using hiPSC-CMs for in vitro cardiotoxicity studies. This review provides a brief overview of techniques that can be used to quantify changes in the active force that cardiomyocytes generate and variations in their inherent stiffness in response to cardiotoxic drugs. It concludes by discussing the application of these tools in understanding how cardiotoxic drugs directly impact the mechanobiology of cardiomyocytes and how cardiomyocytes sense and respond to mechanical load at the cellular level.
Insights
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a better model for studying drug cardiotoxicity. These cells allow for assessing long-term effects on cardiomyocyte contractility and mechanics, improving safety testing.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Toxicology
Background:
- Traditional cardiotoxicity testing uses animal cardiomyocytes with limited viability and physiological relevance.
- Existing methods focus on short-term electrophysiological effects, neglecting long-term mechanical and structural impacts.
- Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) present a more physiologically relevant and viable alternative.
Purpose of the Study:
- To review techniques for quantifying drug-induced changes in cardiomyocyte force generation and stiffness.
- To explore the application of hiPSC-CMs in assessing cardiotoxicity, including mechanobiological effects.
- To enhance understanding of how drugs impact cardiomyocyte mechanobiology and cellular responses to mechanical load.
Main Methods:
- Overview of techniques to measure active force generated by cardiomyocytes.
- Description of methods to assess variations in cardiomyocyte stiffness.
- Utilizing hiPSC-CMs for in vitro cardiotoxicity studies.
Main Results:
- hiPSC-CMs enable the study of both electrophysiological and mechanical/contractile effects of cardiotoxic drugs.
- Quantification techniques reveal drug-induced alterations in cardiomyocyte force and stiffness.
- These methods provide insights into the mechanobiology of cardiotoxicity.
Conclusions:
- hiPSC-CMs are valuable tools for comprehensive in vitro cardiotoxicity assessment.
- Measuring force and stiffness in hiPSC-CMs is crucial for understanding long-term drug effects.
- This approach advances the study of drug-induced mechanobiology in cardiomyocytes.
