The role of Myosin II in Mechanotransduction

National Heart, Lung, And Blood Institute

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Abstract

To investigate the contribution of integrins vs. cadherins signal transduction to early cardiac development we established the microprinting technique. We assess mechanosensation in cardiomyocytes of the early heart (E14.5) during the process of maturation of the contractile system and formation of sarcomeric structures. We test integrin signal transduction by visualizing cardiac cell spreading and development of the adult cytoarchitecture on collagen I (collagen I is a main component of the extracellular matrix) and fibronectin coated micro-patterns on sift and solid acrylamide gels whereas cadherin coated micro-patterns on acrylamide gels provide us with an opportunity to test the role of cell-to-cell mechanotransduction throughout a full range of substrate stiffness. This allows us to elucidate proteins that serve as proper adhesion substrates for cardiomyocytes within normal hearts, and that fail to support robust cell spreading and maturation of the cardiac cells. To assess reproducibility and test the role of mechanical load in the maturation process an independent series of adhesion substrates will be tested. This second series will accommodate treatment with caffeine and norepinephrine to affect gene expression of cardiomyocytes, similar to how it was used for cardiac cell stimulation previously. We will attribute the differences in maturation of early cardiomyocytes on sift and solid adhesion micro-patterns to integrins vs. cadherins signal transduction in the process of sarcomerogenesis which creates a platform for the study of NMII's role in cardiac cell mechanotransduction and cardiac tissue development.