Wang Cheng, Xu Na, Yang Yu-Jun, Wu Qiu-Mei, Pang Dai-Wen, Zhang Zhi-Ling
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, P. R. China.
Integr Biol (Camb). 2017 Dec 11;9(12):903-911. doi: 10.1039/c7ib00151g.
Virus-induced cell migration plays important roles in the direct and rapid spread of virus particles. As cell migration is also regulated by shear stress, it is necessary to explore the cell migration behavior influenced by multiple factors including a virus and shear stress. In this report, a three-layer microfluidic chip with symmetric channels was designed and fabricated to investigate vaccinia virus-induced cell migration in different shear stress environments. Regular "exclusion zones" without cell damage were formed by microvalves. The results showed that infected cells were more elongated and tended to migrate along the flow direction compared to the random cell migration under static conditions. Meanwhile, shear stress enhanced the natural directional persistence and accelerated the velocity of infected cell migration. Moreover, reduced peripheral lamellae and the axial lamella being confined to the flow direction were responsible for the increased directionality of cell migration under shear stress. Interestingly, in the presence of shear stress, the Golgi complex reoriented and relocated behind the nucleus and aligned to the flow direction in infected migratory cells accompanied by the rearrangement of the cytoskeleton. Our report reveals the cell migration behavior in the multi-environment of virus infection and shear stress based on the microfluidic cell migration assay platform. It helps us to deeply understand the interactions between the virus, host cells, and surrounding microenvironment.
病毒诱导的细胞迁移在病毒颗粒的直接和快速传播中起着重要作用。由于细胞迁移也受剪切应力调节，因此有必要探索受病毒和剪切应力等多种因素影响的细胞迁移行为。在本报告中，设计并制造了一种具有对称通道的三层微流控芯片，以研究痘苗病毒在不同剪切应力环境下诱导的细胞迁移。通过微阀形成了没有细胞损伤的规则“排斥区”。结果表明，与静态条件下随机的细胞迁移相比，受感染的细胞更细长，并且倾向于沿流动方向迁移。同时，剪切应力增强了自然的方向持续性并加速了受感染细胞的迁移速度。此外，外周薄片减少以及轴向薄片局限于流动方向是剪切应力下细胞迁移方向性增加的原因。有趣的是，在存在剪切应力的情况下，高尔基体复合体重新定向并重新定位到细胞核后方，并在受感染的迁移细胞中与流动方向对齐，同时伴随着细胞骨架的重新排列。我们的报告基于微流控细胞迁移分析平台揭示了病毒感染和剪切应力多环境中的细胞迁移行为。它有助于我们深入了解病毒、宿主细胞和周围微环境之间的相互作用。
