Tunable Magnetorheological Elastomer Substrates for Studying Mechano-Genetic Interactions in Hypertrophic Cardiomyopathy

Dynamically tunable magnetorheological elastomer stiffening selectively unmasked pathological structural remodeling in hiPSC-derived cardiomyocytes with the HCM-associated MYBPC3fs loss-of-function variant.

• Why it matters: Existing in vitro HCM models use static mechanics, limiting how dynamic loading can be tested for interaction with genetic susceptibility during disease initiation.
• What they did: The study used a dynamically tunable MRE platform to model progressive mechanical stiffening in hiPSC-derived cardiomyocytes carrying MYBPC3fs, comparing effects with isogenic controls.
• The result: In MYBPC3fs cardiomyocytes, mechanical stiffening drove hypertrophic remodeling, sarcomere disorganization, nuclear remodeling, dysregulated NFAT3 signaling, and aberrant cell-cycle activity, and it induced fibroblast-to-myofibroblast transition in primary cardiac fibroblasts.