title: Atomic force mechanobiology of pluripotent stem cell-derived cardiomyocytes.
abstract: We describe a method using atomic force microscopy (AFM) to quantify the mechanobiological properties of pluripotent, stem cell-derived cardiomyocytes, including contraction force, rate, duration, and cellular elasticity. We measured beats from cardiomyocytes derived from induced pluripotent stem cells of healthy subjects and those with dilated cardiomyopathy, and from embryonic stem cell lines. We found that our AFM method could quantitate beat forces of single cells and clusters of cardiomyocytes. We demonstrate the dose-responsive, inotropic effect of norepinephrine and beta-adrenergic blockade of metoprolol. Cardiomyocytes derived from subjects with dilated cardiomyopathy showed decreased force and decreased cellular elasticity compared to controls. This AFM-based method can serve as a screening tool for the development of cardiac-active pharmacological agents, or as a platform for studying cardiomyocyte biology.
authors.affiliation: Department of Pediatrics, Division of Immunology & Allergy, Stanford University, Stanford, California, United States of America.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Marc A
authors.initials: MA
authors.lastname: Bruce
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Butte
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D001696:Biomechanical Phenomena; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D008790:Metoprolol / Q000494:pharmacology; D018625:Microscopy, Atomic Force / Q000379:methods*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D039904:Pluripotent Stem Cells / Q000166:cytology*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D008790:Metoprolol; D009638:Norepinephrine