The effect of substrate stiffness on cardiac performance

The stiffness of the human myocardium increases as part of the ageing process, which is associated with a higher risk of ventricular pathologies such as heart failure with preserved ejection fraction (HFpEF), especially in elderly in the presence of co- morbidities. Increased deposition of extracellular matrix proteins, particularly collagens, are believed to drive increased cardiac stiffness. However, the mechanisms underlying increased myocardial stiffness are not entirely understood. The objectives of this project are to model increased matrix stiffness in vitro, and investigate the effects of matrix stiffness on induced pluripotent cardiomyocyte biology, electrophysiology and metabolism. The effect of substrate stiffness onto cardiomyocyte performance will be assessed by contractility measurements and electrophysiological assays.