The heart is not a regenerative organ. The premature loss of heart cells or cardiomyocytes leads to fibrosis and structural remodeling of the heart. These changes stiffen the heart tissue, compromising heart function. We are mimicking diseased heart tissue by micropatterning cardiomyocytes on hydrogels that have the stiffness of a fibrotic heart. By understanding the crosstalk between mechanical stress and molecular signals that contribute to disease, we can identify targets for intervention.