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Contractility Drives Cardiomyocyte Maturation and the Response to Nanopatterns
Laura A Sherer1, Abigail Nagle2, Mary Papadaki3
1Section of Cardiology, Biological Sciences Division, Department of Medicine, University of Chicago, IL (L.A.S., M.Q., J.A.K.).
Circulation Research
|July 9, 2026
Summary
Calcium-activated contractility is not essential for sarcomere formation in stem cell-derived cardiomyocytes but is crucial for their maturation. External mechanical cues can partially improve maturation in noncontractile cells.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Cellular Mechanics
Background:
- Understanding cardiomyocyte development is key for induced pluripotent stem cell (iPSC)-derived cardiomyocytes.
- Mechanical cues influence myocyte development, but their integration is not fully understood.
- This study investigates calcium-activated contractility's role in sarcomere formation and maturation.
Purpose of the Study:
- To examine the role of calcium-activated contractility in sarcomere formation and maturation.
- To assess the influence of contractility on iPSC-derived cardiomyocyte response to nanopatterns.
- To elucidate how external mechanical signals affect maturation in contractile versus noncontractile cells.
Main Methods:
- Generated iPSCs with engineered cardiac troponin C (cTnC) lacking calcium binding at site II (D65A cTnC), inhibiting contraction.
- Differentiated iPSCs into cardiomyocytes and matured them for 60 days, analyzing structure, metabolism, and calcium transients.
- Examined proteomes via mass spectrometry and replated cells onto nanopatterns to test mechanical signal influence.
Main Results:
- Sarcomeres formed in D65A cTnC cardiomyocytes but were underdeveloped and disorganized.
- D65A cardiomyocytes showed proteomic maturation defects and abnormal calcium transients.
- Nanopatterns improved maturation metrics in noncontractile cells, but not in wild-type cells.
Conclusions:
- Calcium-activated contractility is dispensable for sarcomerogenesis but critical for cardiomyocyte maturation.
- External mechanical cues (nanopatterns) can partially compensate for defective contractility.
- Mature cardiomyocytes may be less responsive to nanopattern-mediated maturation cues.
