Extracellular matrix composition controls the development of alternans in cardiac tissue

The integrity and functionality of all living tissue highly depends on their embedding in the extracellular matrix (ECM). It provides cells with a certain rigidity and various types of proteins to ensure stability, nutrition and anchorage of the single cells and tissue. These properties highly impact all tissue types, including the here discussed heart tissue. In cardiac muscle, tissue stiffness plays an especially critical role, since it can impair regular functions by disturbing natural electrophysiological conduction. An often discussed but not entirely understood subject is alternans. It is commonly ac-cepted that alternans can pathologically disturb natural cardiac rhythms and thereby lead to life-threatening medical conditions. Previous studies have gained insights on the influence of cardiac tissue stiffness on electrophysiological dynamics, but details about their formation remain to be elucidated. Here, we address the effects of variations in the ECM rigidity and matrix protein composition on the cardiac tissue morphology and dynamic alternans patterns. Employing a combination of high-speed life imaging, classical fluorescence staining and machine learning algorithms, we elucidate the critical relationship between tissue morphology and electromechanical dynamics. Clinical Relevance-Using high-speed life imaging, this work aims at understanding the connection between tissue morphology, ECM composition and alternans dynamics in healthy and diseased heart tissues for possible future applications, treatments and prediction of cardiac diseases.