Evidence map›Paper›PMID 42422954›Full record

ArticleCirculation research2026

Contractility Drives Cardiomyocyte Maturation and the Response to Nanopatterns.

Laura A Sherer, Abigail Nagle, Maria Papadaki, Seby L Edassery, Timothy S McMillen, Dasom Yoo, Lauren D'Amico, Daniel Brambila-Diaz, Lucy Maynard, Mark Qiao and 3 more

Abstract read
In one paragraph

Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Laura A Sherer *Section of Cardiology, Biological Sciences Division, Department of Medicine, University of Chicago, IL (L.A.S., M.Q., J.A.K.).
Abigail Nagle *Department of Laboratory Medicine and Pathology (A.N., J.D.), University of Washington, Seattle, WA.ORCID 0000-0002-6200-8628
Maria PapadakiDepartment of Cell and Molecular Physiology, Loyola University Stritch School of Medicine, Maywood, IL (M.P., S.L.E.).ORCID 0000-0001-8903-7085
Seby L EdasseryDepartment of Cell and Molecular Physiology, Loyola University Stritch School of Medicine, Maywood, IL (M.P., S.L.E.).ORCID 0000-0003-1129-748X
Timothy S McMillenDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.ORCID 0000-0001-5261-3229
Dasom YooDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.
Lauren D'AmicoDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.ORCID 0000-0002-7142-472X
Daniel Brambila-DiazDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.
Lucy MaynardDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.ORCID 0000-0001-9135-6755
Mark QiaoSection of Cardiology, Biological Sciences Division, Department of Medicine, University of Chicago, IL (L.A.S., M.Q., J.A.K.).
Jennifer DavisDepartment of Laboratory Medicine and Pathology (A.N., J.D.), University of Washington, Seattle, WA.ORCID 0000-0003-2380-1321
Michael RegnierDepartment of Bioengineering (T.S.M., D.Y., L.D., D.B.-D., L.M., J.D., M.R.), University of Washington, Seattle, WA.ORCID 0000-0001-5437-9851
Jonathan A KirkSection of Cardiology, Biological Sciences Division, Department of Medicine, University of Chicago, IL (L.A.S., M.Q., J.A.K.).ORCID 0000-0002-5192-2860

Funding

UW Center for Translational Muscle Research (Overall Application)P30AR074990 · NIAMS · UNIVERSITY OF WASHINGTON · PI Jennifer Michelle Davis · 2019 to 2026
$7.5M
Engineered Stem Cells for Cardiac RepairR01HL128368 · NHLBI · UNIVERSITY OF WASHINGTON · PI REGNIER, MICHAEL · 2018 to 2025
$6.1M
GSK-3β Localizes to the Myofilament and Modifies its Function in Ischemic CardiomyopathyR01HL136737 · NHLBI · UNIVERSITY OF CHICAGO · PI JONATHAN A KIRK · 2017 to 2026
$4.5M
Broadly applicable high throughput variant interpretation and validation for MYH7R01HL175964 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI JONATHAN A KIRK, Md. Abul Hassan Samee · 2024 to 2026
$2.1M
Structural and functional basis of myocardial dysregulation in genetic cardiomyopathyR01HL172492 · NHLBI · UNIVERSITY OF CHICAGO · PI THOMAS C IRVING, JONATHAN A KIRK · 2024 to 2026
$2.1M
An Investigation of Focal Adhesion Tension During Cardiomyocyte ContractionF31HL163921 · NHLBI · UNIVERSITY OF WASHINGTON · PI NAGLE, ABIGAIL · 2022 to 2024
$124k
NHLBI NIH HHS F31 HL163921NHLBI NIH HHS R01 HL128368NHLBI NIH HHS R01 HL136737NHLBI NIH HHS R01 HL172492NHLBI NIH HHS R01 HL175964NIAMS NIH HHS P30 AR074990
6 · The paper itself

Abstract

backgroundUnderstanding the mechanisms of cardiomyocyte development is critical for fulfilling the potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Although myocyte development is known to depend on internal and external mechanical cues, further investigation is required to understand the contributions of different signals and how they are integrated together to generate an adult cardiomyocyte. Here, we address this gap by examining the role of calcium-activated contractility in sarcomere formation and maturation and its influence on the iPSC-CM response to nanopatterns.

methodsWe generated iPSCs with homozygous D65A cTnC (cardiac troponin C) substitutions. This engineered cTnC cannot bind to calcium at site II, resulting in tropomyosin blocking strong myosin binding to the thin filament and inhibiting sarcomere contraction. The iPSCs were differentiated into cardiomyocytes and matured in culture over 60 days. Cells were characterized via imaging, metabolic assays, and calcium transient analysis. Proteomes were examined using mass spectrometry throughout differentiation and maturation. We also replated partially matured cardiomyocytes onto nanopatterned surfaces to investigate how external mechanical signals affect maturation in contractile versus noncontractile cells.

resultsSurprisingly, we found that sarcomeres formed in the D65A cTnC cardiomyocytes, though these sarcomeres were underdeveloped and disorganized. The D65A cardiomyocytes also exhibited significant proteomic maturation defects and abnormal calcium transients. Replating the noncontractile cardiomyocytes onto nanopatterns improved several structural and proteomic maturation metrics. In contrast, wildtype maturation did not benefit from the introduction of nanopatterns.

conclusionsCalcium-activated contractility is dispensable for sarcomerogenesis but critical for cardiomyocyte maturation. In noncontractile, D65A cTnC cardiomyocytes, nanopatterns enhanced maturation, suggesting that external mechanical cues may partially compensate for defective contractility. However, nanopatterns did not facilitate wildtype maturation, suggesting that maturity may reduce the efficacy of nanopatterns. In addition to these novel findings, these mass spectrometry data sets cataloging iPSC-CM maturation represent a useful resource for the cardiovascular research community.

Indexed as

Cell DifferentiationInduced Pluripotent Stem CellsMyocardial ContractionMyocytes, CardiacAnimalsCalciumCalcium SignalingCells, CulturedHumansSarcomeresTroponin CCalciumTroponin Chuman induced pluripotent stem cellsmass spectrometrymyocytes, cardiacproteomicssarcomeres

Identifiers

PMID42422954
PMCPMC13437040

What Socratic holds

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Registered trials

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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 Socratic graph.