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

• Published in: Lab on a chip 2023-08, Vol.23 (16), p.3581-3592
• Main Authors: Yang, Hao, Chen, Tao, Hu, Yichong, Niu, Fuzhou, Zheng, Xinyu, Sun, Haizhen, Cheng, Liang, Sun, Lining
• Format: Article
• Language: English
• Subjects: Biomechanics; Cell culture; Cell Culture Techniques; Cytoskeleton; Dielectrophoresis; Elastic properties; Endothelial cells; Endothelium; Hemodynamics; Human Umbilical Vein Endothelial Cells; Humans; In situ measurement; Mechanical properties; Microfluidics; Modulus of elasticity; Multilayers; Physiological effects; Physiological factors; Physiology; Shear modulus; Shear stress; Stress, Mechanical; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/d3lc00363a

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 , which is labor-intensive and time-consuming. Notably, many physiological factors are lacking in Petri dish culture compared with 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 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.