(577a) Structure-Function Relationships in Cardiac Myocytes*

Posttranscriptional processes such as translation or signaling pathways contribute to regulation of muscle growth during cardiac organo- and pathogenesis. However, little is known about the mechanisms and signals that potentiate directional muscle growth and the self-assembly of sarcomeres and myofibrils. These structures appear to be optimized for their contractile function. In order to elucidate the structure-function relationships that govern contractility, we use microfabrication techniques to build engineered cardiac myocytes from neonatal rat ventricular myocytes. By controlling only the 2D boundary conditions imposed on the myocyte, we are able to engineer predictable myofibrillar patterns and contractility of individual myocytes. These experiments have revealed how the extracellular matrix potentiates the self-assembly of the myocyte cytoskeleton architecture which serves as a template for myofibrillar patterning. Our results suggest the post-translational mechanisms that regulate myofibrillogenesis in the developing myocyte and whose perturbation lead to contractile dysfunction in the diseased heart.