ArticlePLoS computational biology2016
Mechano-chemical Interactions in Cardiac Sarcomere Contraction: A Computational Modeling Study.
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.The Journal of general physiology · 2025Article
- Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.Circulation. Heart failure · 2023Article
- From evidence-based medicine to digital twin technology for predicting ventricular tachycardia in ischaemic cardiomyopathy.Journal of the Royal Society, Interface · 2022Article
- A NovelFrontiers in physiology · 2022Article
- Biophysically detailed mathematical models of multiscale cardiac active mechanics.PLoS computational biology · 2020Article
- Cardiac muscle regulatory units are predicted to interact stronger than neighboring cross-bridges.Scientific reports · 2020Article
- Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model.The journal of physiological sciences : JPS · 2020Article
- Stretch-activated current in human atrial myocytes and NaBiomedical engineering online · 2019Article
- Article
- Titin-mediated thick filament activation, through a mechanosensing mechanism, introduces sarcomere-length dependencies in mathematical models of rat trabecula and whole ventricle.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We developed a model of cardiac sarcomere contraction to study the calcium-tension relationship in cardiac muscle. Calcium mediates cardiac contraction through its interactions with troponin (Tn) and subsequently tropomyosin molecules. Experimental studies have shown that a slight increase in intracellular calcium concentration leads to a rapid increase in sarcomeric tension. Though it is widely accepted that the rapid increase is not possible without the concept of cooperativity, the mechanism is debated. We use the hypothesis that there exists a base level of cooperativity intrinsic to the thin filament that is boosted by mechanical tension, i.e. a high level of mechanical tension in the thin filament impedes the unbinding of calcium from Tn. To test these hypotheses, we developed a computational model in which a set of three parameters and inputs of calcium concentration and sarcomere length result in output tension. Tension as simulated appeared in good agreement with experimentally measured tension. Our results support the hypothesis that high tension in the thin filament impedes Tn deactivation by increasing the energy required to detach calcium from the Tn. Given this hypothesis, the model predicted that the areas with highest tension, i.e. closest to the Z-disk end of the single overlap region, show the largest concentration of active Tn's.
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