Development of a set up for the combined measurement of force, myocyte tension and mitochondrial redox status in rat engineered heart tissue to characterize cardiac hypertro

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The aim of this project is the establishment of a new setup that allows the measurement of two important parameters in heart biology in electrically stimulated engineered heart tissues - myocyte tension (as a surrogate for wall stress in whole hearts) and mitochondrial redox status. Both will be measured on a fluorescence-based technique in parallel to the developed force of the artificial heart muscle. For myocyte tension, a FRET-based imaging system that visualizes the interaction between the mechanosensitive apelin receptor and beta-arrestine will be established. A modified red fluorescent protein with a mitochondrial recognition sequence will be used to visualize the mitochondrial redox status. The system will provide measurements of the influence of different pre- and afterload as well as pharmacological modification of myofilament calcium sensitivity on myocyte tension and the mitochondrial redox status in work-performing heart muscles. Wall stress and mitochondrial redox status likely play an important, but still incompletely understood role in the pathogenesis of cardiac hypertrophy and genetically determined cardiomyopathies. The successful outcome of this project might lead to novel insights in these important biological processes leading to cardiac hypertrophy.