Robotics and Microsystems Center, College of Mechanical and Electrical Engineering, Soochow University, Suzhou 215000, China.
School of Mechanical Engineering, Suzhou University of Science and Technology, Suzhou 215000, China.
Lab Chip. 2023 Aug 8;23(16):3581-3592. 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.
血管内皮细胞 (ECs) 在复杂的血管微环境中的功能通常受到生化线索、细胞间相互作用和流体切应力的调节。这些调节因子在决定细胞力学特性方面起着至关重要的作用，如弹性和剪切模量，这些参数对于评估细胞状态非常重要。然而，大多数关于细胞力学特性测量的研究都是在 条件下进行的，这是一项劳动密集型且耗时的工作。值得注意的是，与体内环境相比，培养皿中的许多生理因素都缺乏，导致结果不准确，临床相关性差。在此，我们开发了一种多层微流控芯片，它集成了动态细胞培养、操作和介电泳测量力学特性。此外，我们通过数值和实验模拟了血管微环境，研究了流速和肿瘤坏死因子-α (TNF-α) 对人脐静脉内皮细胞 (HUVECs) 杨氏模量的影响。结果表明，较大的流体切应力导致 HUVECs 的杨氏模量增加，这表明血液动力学在调节 ECs 的生物力学方面的重要性。相比之下，TNF-α 是一种炎症诱导剂，可显著降低 HUVEC 的硬度，表明其对血管内皮有不利影响。细胞松弛素 D，一种细胞骨架破坏剂，可显著降低 HUVEC 的杨氏模量。总之，所提出的血管模拟动态培养和监测方法可促进 ECs 在器官芯片微系统中的生理发育，从而准确有效地研究心血管疾病中的血液动力学和药理学机制。
