Abstract 13443: Function Follows Form: Shape and Substrate Stiffness Drive Maturity in Human Cardiomyocytes Differentiated From Pluripotent Stem Cells

Introduction: Heart function relies on the contractility of its muscle cells (cardiomyocytes). Human pluripotent stem cells (hPSC) can be differentiated into cardiomyocytes (hPSC-CMs). However, while their myogenic maturity increases with time, they do not resemble adult cardiomyocytes in their morphology, structural organization, mechanical output and electrophysiology. The low maturity of hPSC-CMs limits their potential to model, study and treat heart diseases. Hypothesis: Since the organization of sarcomeres regulates the mechanical output of cardiomyocytes, we hypothesized that enhanced sarcomere maturity correlates with the mechanical output of these cells and the physiology of matured cardiomyocytes. Methods: We cultured single hPSC-CMs on 2000 μm2 rectangular protein patterns on polyacrylamide substrates with a modulus of 10 kPa to resemble the morphology of ventricular cardiomyocytes and match healthy adult ventricular stiffness. We infected seeded cells with rAV CAG-LifeAct-Tag RFP to label actin...