Actuating Extracellular Matrices Decouple the Mechanical and Biochemical Effects of Muscle Contraction on Motor Neurons.

Emerging in vivo evidence suggests that repeated muscle contraction, or exercise, impacts peripheral nerves. However, the difficulty of isolating the muscle-specific impact on motor neurons in vivo, as well as the inability to decouple the biochemical and mechanical impacts of muscle contraction in this setting, motivates investigating this phenomenon in vitro. This study demonstrates that tuning the mechanical properties of fibrin enables longitudinal culture of highly contractile skeletal muscle monolayers, enabling functional characterization of and long-term secretome harvesting from exercised tissues.

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.

Elastomer-Grafted iPSC-Derived Micro Heart Muscles to Investigate Effects of Mechanical Loading on Physiology.

Mechanical loading plays a critical role in cardiac pathophysiology. Engineered heart tissues derived from human induced pluripotent stem cells (iPSCs) allow rigorous investigations of the molecular and pathophysiological consequences of mechanical cues. However, many engineered heart muscle models have complex fabrication processes and require large cell numbers, making it difficult to use them together with iPSC-derived cardiomyocytes to study the influence of mechanical loading on pharmacology and genotype-phenotype relationships.