Using novel tools to understand disease states in heart cells ‘in a dish’

The cells that make up the contractile tissue of the heart, the cardiomyocytes, need two multiprotein complexes to do their job, the myofibrils, which mediate contraction and the intercalated discs, the key site for electromechanical linkage between cells. These multiprotein complexes are strongly affected during heart disease. Understanding why this happens needs good model systems that can recapitulate the disease in vitro. To achieve this, we want to use cardiomyocytes in a culture dish, that mimic well cardiomyocytes in vivo, and that we can manipulate to shed more light on disease mechanisms. We will use designer molecules (Adhirons) on primary rat cardiomyocytes and iPSC-cardiomyocytes to disrupt protein-protein interactions of key players. Using specialised designer bioenvironments to grow the cells will guarantee more transferable results by limiting artefacts. The expected findings will contribute to our understanding of heart disease and help to discover new drug targets.