Understanding spatiotemporal mechanical behavior, viscoelasticity, and functions of stem cell-derived cardiomyocytes.

Understanding myocytes' spatiotemporal mechanical behavior and viscoelasticity is a long-standing challenge as it plays a critical role in regulating structural and functional homeostasis. To probe the time-dependent viscoelastic behaviors of cardiomyocytes with cross-linked polymer networks, we measure stem cell-derived cardiomyocyte's (hiPSC-CM) deformation, adhesion, and contractility using atomic force microscopy (AFM) nanoindentation, fluidic micropipette, and digital image correlation (DIC). Our results show a cytoplasm load of 7-14 nN, a de-adhesion force of 0.1-1 nN, and an adhesion force between two hiPSC-CMs of 50-100 nN with an interface energy of 0.45 pJ. Based on the load-displacement curve, we model its dynamic viscoelasticity and discover its intimate associations with physiological properties. Cell detaching and contractile modeling demonstrate cell-cell adhesion and beating related strains manifesting viscoelastic behavior, highlighting viscoelasticity plays the primary role in governing hiPSC-CM spatiotemporal mechanics and functions. Overall, this study provides valuable information about the mechanical properties, adhesion behaviors, and viscoelasticity of single hiPSC-CM, shedding light on mechanical-structure relationships and their dynamic responses to mechanical stimuli and spontaneous contraction.