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A microfluidic platform integrating dynamic cell culture and dielectrophoretic manipulation for in situ assessment of endothelial cell mechanics

脐静脉 细胞生物学 剪应力 机械生物学 内皮干细胞 细胞培养 微流控 化学 生物医学工程 生物物理学 材料科学 纳米技术 体外 医学 生物 生物化学 复合材料 遗传学
作者
Hao Yang,Tao Chen,Yichong Hu,Fuzhou Niu,Xinyu Zheng,Haizhen Sun,Liang Cheng,Lining Sun
出处
期刊:Lab on a Chip [Royal Society of Chemistry]
卷期号:23 (16): 3581-3592 被引量:2
标识
DOI:10.1039/d3lc00363a
摘要

The function of vascular endothelial cells (ECs) within the complex vascular microenvironment is typically modulated by biochemical cues, cell-cell interactions, and fluid shear stress. These regulatory factors play a crucial role in determining cell mechanical properties, such as elastic and shear moduli, which are important parameters for assessing cell status. However, most studies on the measurement of cell mechanical properties have been conducted in vitro, which is labor-intensive and time-consuming. Notably, many physiological factors are lacking in Petri dish culture compared with in vivo conditions, leading to inaccurate results and poor clinical relevance. Herein, we developed a multi-layer microfluidic chip that integrates dynamic cell culture, manipulation and dielectrophoretic in situ measurement of mechanical properties. Furthermore, we numerically and experimentally simulated the vascular microenvironment to investigate the effects of flow rate and tumor necrosis factor-alpha (TNF-α) on the Young's modulus of human umbilical vein endothelial cells (HUVECs). Results showed that greater fluid shear stress results in increased Young's modulus of HUVECs, suggesting the importance of hemodynamics in modulating the biomechanics of ECs. In contrast, TNF-α, an inflammation inducer, dramatically decreased HUVEC stiffness, demonstrating an adverse impact on the vascular endothelium. Blebbistatin, a cytoskeleton disruptor, significantly reduced the Young's modulus of HUVECs. In summary, the proposed vascular-mimetic dynamic culture and monitoring approach enables the physiological development of ECs in organ-on-a-chip microsystems for accurately and efficiently studying hemodynamics and pharmacological mechanisms underlying cardiovascular diseases.
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