Cardiovascular diseases are notoriously complex in their etiologies and progressions. For this reason, treatments remain limited, and CVDs continue to be the leading cause of death globally. Historically, CVDs have been studied using animal models, but there is an increasing need for robust, translational in vitro approaches to model human-specific pathophysiology and drug response. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising direction towards this goal, but they tend to exhibit limited maturation potential in culture. Two main culture conditions that influence this potential are the substrate that the cells adhere to, and the biochemical/physical cues communicated by added ECM proteins. Recent work has shown that substrate stiffness is one particular factor that can have an effect in this regard. This project aims to screen, identify, and characterize combinations of substrate stiffness and ECM proteins that can support hiPSC-CM cultures. Through an algorithm-directed optimization approach, we hope to uncover potential interactions between these factors and their role in directing cardiomyocyte maturation.