Key result
Dynamic mechanical stress exacerbates sarcomeric and contractile defects in MYBPC3- and BAG3-deficient hiPSC-CMs.
Why the study?
Cardiomyocyte mechanobiology studies typically rely on static systems that fail to capture the progressive nature of native cardiac remodeling.
Dynamic mechanical stress exacerbates sarcomere failure and contractile dysfunction in hiPSC-CMs with cardiomyopathy-associated MYBPC3 and BAG3 mutations, highlighting the synergistic role of genetic vulnerability and mechanical load.
Mechanical stress may worsen sarcomere defects in MYBPC3/BAG3 cardiomyopathy; hypothesis-generating for load modulation, pending in vivo confirmation.
: Mechanical stress plays a critical role in regulating cardiomyocyte structure and physiology. However, mechanobiology studies still rely on static systems that failed to capture the progressive nature of native cardiac remodeling. Building on our prior shape memory polymer (SMP)-based platform, the present study integrates microcontact printing onto SMP substrates to achieve single-cell geometric control and on-demand dynamic mechanical modulation. Using CRISPR/Cas9-engineered MYBPC3- and BAG3-mutant hiPSC-CMs along with isogenic wild-type (WT) control, we systematically assessed sarcomere organization and contractile behavior under static and dynamic mechanical conditions. WT hiPSC-CMs displayed robust morphological adaptability and coordinated sarcomere remodeling in response to dynamic mechanical cues, whereas MYBPC3- and BAG3-deficient hiPSC-CMs exhibited mutation-specific defects in sarcomere integrity and contractile behavior that were exacerbated by dynamic mechanical stress. These results demonstrate that his SMP-based platform enables us to systematically compare genotype-based mechanical sensitivity to develop more severe cardiomyopathy phenotypes.
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Wang et al. (2026) studied Cardiomyopathy (in vitro model). Dynamic mechanical stress via shape memory polymer platform vs. Static mechanical conditions was evaluated on Sarcomere organization and contractile behavior. Dynamic mechanical stress exacerbated mutation-specific defects in sarcomere integrity and contractile behavior in MYBPC3- and BAG3-deficient hiPSC-CMs compared to wild-type controls.
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