ArticleProceedings of the National Academy of Sciences of the United States of America2015
Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 297 papers, 2 of them syntheses that pooled it.
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Who cites it
297 citing papers in PubMed, 2 syntheses or guidelines pooled it, 477 citations in OpenAlex.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Towards chamber specific heart-on-a-chip for drug testing applications.Advanced drug delivery reviews · 2020Pooled it
- Genetic vulnerability and dynamic mechanical stress synergistically drive sarcomere failure in human iPSC-derived cardiomyocytes.Materials today. Bio · 2026Article
- Optical Detection of Cellular Signals at Material Interfaces.Advanced healthcare materials · 2026Review
- Sarcomere dynamic instability and stochastic heterogeneity drive robust cardiomyocyte contraction.eLife · 2026Article
- Proteogenomics of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy.Circulation research · 2026Observational
- Review
- Integrative circulatory engineering for regenerative therapy: Dynamic perfusion design and metabolic maturation in cardiac tissue engineering.Regenerative therapy · 2026Article
- Beta2-adrenergic receptor activation increases susceptibility to arrhythmogenesis in aging heart by impairing repolarization reserve via GScientific reports · 2026Article
- Cardiac-Derived ECM Microspheres for Enhanced hiPSC-CMs Maturation.Advanced functional materials · 2026Article
- The hypertrophic cardiomyopathy myosin variant G256E prolongs cardiac muscle relaxation via altered nucleotide handling.Communications chemistry · 2026Article
- Microgroove and Cyclic Stretch-Based Stem Cell Gym Enhance Maturation of Human iPSC-Derived Cardiomyocytes.Annals of biomedical engineering · 2026Article
- Linking Experimental Models to Pathophysiology: Oxidative Stress and DNA Damage in Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- A Generative AI Framework to Predict Cardiomyocyte Contraction Function from Single Static Images.bioRxiv : the preprint server for biology · 2026Article
- Cell shape and maturation impacts α-actinin-2 tension in iPSC-derived cardiomyocytes.APL bioengineering · 2026Article
- Toward continuous monitoring systems: emerging trends of on-chip sensors in organ-on-a-chip.Microsystems & nanoengineering · 2026Review
- Telomere shortening in laminopathic dilated cardiomyopathy.NPJ Regenerative medicine · 2026Article
- Heart-On-a-Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell- and Tissue-Scale Contractile Stresses.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- High-Throughput Methods for Variant Functional Assessment in Cardiac Disease.Circulation. Genomic and precision medicine · 2026Review
- Functional interrogation of contextually correct MYH7 variants using CRaTER-flox gene editing and contractility profiling.The Journal of clinical investigation · 2026Article
237 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel micropatterns were used to generate physiological shapes (2,000-µm(2) rectangles with length:width aspect ratios of 5:1-7:1) and a mature alignment of myofibrils. Translation of sarcomere shortening to mechanical output was highest in 7:1 hPSC-CMs. Increased substrate stiffness and applied overstretch induced myofibril defects in 7:1 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle myosin activity repressed the assembly of myofibrils, showing that subcellular tension drives the improved contractile activity in these engineered hPSC-CMs. Other factors associated with improved contractility were axially directed calcium flow, systematic mitochondrial distribution, more mature electrophysiology, and evidence of transverse-tubule formation. These findings support the potential of these engineered hPSC-CMs as powerful models for studying myocardial contractility at the cellular level.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.