收缩性
诱导多能干细胞
细胞生物学
肌节
材料科学
拉伤
体内
延伸率
刺激
肌球蛋白
体外
生物
心肌细胞
生物物理学
化学
生物医学工程
解剖
胚胎干细胞
生物化学
神经科学
基因
医学
内分泌学
生物技术
冶金
极限抗拉强度
作者
Wenkun Dou,Li Wang,Manpreet Malhi,Haijiao Liu,Qili Zhao,Julia Plakhotnik,Zhenghua Xu,Zongjie Huang,Craig A. Simmons,Jason T. Maynes,Yu Sun
标识
DOI:10.1016/j.bios.2020.112875
摘要
The use of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as an in vitro model of the heart is limited by their structurally and functionally immature phenotypes. During heart development, mechanical stimuli from in vivo microenvironments are known to regulate cardiomyocyte gene expression and maturation. Accordingly, protocols for culturing iPSC-CMs have recently incorporated mechanical or electromechanical stimulation to induce cellular maturation in vitro; however, the response of iPSC-CMs to different mechanical strain magnitudes is unknown, and existing techniques lack the capability to dynamically measure changes to iPSC-CM contractility in situ as maturation progresses. We developed a microdevice platform which applies cyclical strains of varying magnitudes (5%, 10%, 15% and 20%) to a monolayer of iPSC-CMs, coincidentally measuring contractile stress during mechanical stimulation using fluorescent nanobeads embedded in the microdevice's suspended membrane. Cyclic strain was found to induce circumferential cell alignment on the actuated membranes. In situ contractility measurements revealed that cyclic stimulation gradually increased cardiomyocyte contractility during a 10-day culture period. The contractile stress of iPSC-CM monolayers was found to increase with a higher strain magnitude and plateaued at 15% strain. Cardiomyocyte contractility positively correlated with the elongation of sarcomeres and an increased expression of β-myosin heavy chain (MYH7) in a strain magnitude-dependent manner, illustrating how mechanical stress can be optimized for the phenotypic and proteomic maturation of the cells. iPSC-CMs with improved maturity have the potential to create a more accurate heart model in vitro for applications in disease modeling and therapeutic discovery.
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