Differential Myocyte Response to Strain Vectors and Rate

University Of Illinois At Chicago, Chicago IL

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Abstract

DESCRIPTION (provided by applicant): Biomechanical forces play a dynamic role in cardiac muscle adaptation and disease. Mechanical deformation includes tensile, compressive, and shear stress. There is growing evidence that cells discriminate different vectors of mechanical stress and rate of application. However, the mechanism by which cells detect complex cyclic mechanical stimulus is poorly understood. Phosphorylation and translocation of proteins associated with the costamere or z-disc may mediate mechanotransduction of vector forces and rates of stress and include focal adhesion kinase (FAK), Rho kinase A (Rho), and protein kinase C (PKC). Insufficient data exists on the behavior of these proteins in cardiac muscle to mechanical strain vectors and even less in the response to strain application rates. Therefore, the hypothesis is that the direction and rate of mechanical strain regulates protein phosphorylation and localization in cardiac myocytes. Orienting cells will direct the delivery of strain vectors by plating rat neonatal cardiac myocytes on novel three-dimensional substrata. Western blotting and immunocytochemistry will evaluate phosphorylation and localization of FAK, Rho, and PKCepsilon to cyclic mechanical activity.