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

Abstract

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.