ArticleProceedings of the National Academy of Sciences of the United States of America2016
Mechanical signaling coordinates the embryonic heartbeat.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Co-culturing hiPSC-cardiomyocytes and cardiac fibroblasts enhances engineered heart tissue structure and function.Stem cells translational medicine · 2026Article
- Coordination of cardiogenesis in vivo and in vitro.Nature reviews. Molecular cell biology · 2026Review
- Fiber recruitment drives a phase transition of cell polarization at a critical cell spacing in matrix-mediated tissue remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Water-Soluble Molecular Wires for Membrane Potential Imaging.Angewandte Chemie (International ed. in English) · 2025Article
- Application of human cardiac organoids in cardiovascular disease research.Frontiers in cell and developmental biology · 2025Review
- Harmonic resonance and entrainment of propagating chemical waves by external mechanical stimulation in BZ self-oscillating hydrogels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Harnessing molecular mechanism for precision medicine in dilated cardiomyopathy caused by a mutation in troponin T.bioRxiv : the preprint server for biology · 2024Article
- Investigating the effects of microstructural changes induced by myocardial infarction on the elastic parameters of the heart.Biomechanics and modeling in mechanobiology · 2023Article
- Local tissue mechanics control cardiac pacemaker cell embryonic patterning.Life science alliance · 2023Article
- Cells and Materials for Cardiac Repair and Regeneration.Journal of clinical medicine · 2023Review
- Cardiac fibroblasts and mechanosensation in heart development, health and disease.Nature reviews. Cardiology · 2023Review
- TheFrontiers in physiology · 2023Article
- Following the Beat: Imaging the Valveless Pumping Function in the Early Embryonic Heart.Journal of cardiovascular development and disease · 2022Review
- Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling.Annual review of physiology · 2022Review
- Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function.Frontiers in physiology · 2022Article
- What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm.Biophysical reviews · 2021Review
- Passive myocardial mechanical properties: meaning, measurement, models.Biophysical reviews · 2021Review
- Reconstructing the heart using iPSCs: Engineering strategies and applications.Journal of molecular and cellular cardiology · 2021Review
- Vascularisation of pluripotent stem cell-derived myocardium: biomechanical insights for physiological relevance in cardiac tissue engineering.Pflugers Archiv : European journal of physiology · 2021Review
- Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine.The Journal of general physiology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts-consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats.
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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.