atomic force mechanobiology of pluripotent stem cell-derived cardiomyocytes原子力力学生物学的多能干细胞心肌细胞.pdfVIP

Atomic Force Mechanobiology of Pluripotent Stem Cell- Derived Cardiomyocytes 1. 2. 1 2 1 Jianwei Liu , Ning Sun , Marc A. Bruce , Joseph C. Wu , Manish J. Butte * 1 Department of Pediatrics, Division of Immunology Allergy, Stanford University, Stanford, California, United States of America, 2 Department of Medicine, Division of Cardiology, Stanford University, Stanford, California, United States of America 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. Citation: Liu J, Sun N, Bruce MA, Wu JC, Butte MJ (2012) Atomic Force Mechanobiology of Pluripotent Stem Cell-Derived Cardiomyocytes. PLoS ONE 7(5): e37559. doi:10.1371/journal.pone.0037559 Editor: Daniel J. Muller, Swiss Federal Institute of Technology Zurich, Switzerland Received December 25, 2011; Accepted April 25, 2012; Published May 18, 2012 Co