Interplay of Genotype and Substrate Stiffness in Driving the Hypertrophic Cardiomyopathy Phenotype in iPSC-Micro-Heart Muscle Arrays.

Introduction: In clinical and animal studies, Hypertrophic Cardiomyopathy (HCM) shares many similarities with non-inherited cardiac hypertrophy induced by pressure overload (hypertension). This suggests a potential role for mechanical stress in priming tissues with mutation-induced changes in the sarcomere to develop phenotypes associated with HCM, including hypercontractility and aberrant calcium handling. Here, we tested the hypothesis that heterozygous loss of function of Myosin Binding Protein C (MYBCP3 , mutations in which account for almost 50% of inherited HCM) combines with environmental stiffness to drive HCM phenotypes.