Analysis of the biomechanical properties of induced pluripotent stem cells from patients with congenital heart disease induced by titin mutations

The goal of this project is to investigate the biomechanical properties (e.g. cell elasticity, contractility and organization of the cytoskeleton) of patient-specific and CRISPR-engineered induced pluripotent stem cells (iPSCs) with cardiac impairments induced by titin mutations. These properties will be analyzed under physiological and pharmacological conditions in diseased as well as in isogenic control cardiomyocytes using biophysical techniques. The results will serve to better understand the basic functionality of the respective cardiac cells, the disease mechanisms and potentially, to lead to targeted therapies. Stem Cell Unit at DZHK partner site Göttingen possesses numerous iPSC lines with various genetically caused cardiac diseases and a long-lasting experience in generation of iPSC-derived functional cardiomyocytes and in developing tissue engineered heart muscles as a potential treatment option in heart failure. The biophysical tools available in Greifswald (e.g. atomic force microscopy, colloidal probe techniques, confocal microscopy), together with the iPSC expertise of our cooperation partners in Göttingen provide all the premises for the successful implementation of this project.