Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 37673, Korea.
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH) San 31, Hyoja-dong, Nam-Gu, Pohang, Gyeongbuk, 37673, Korea.
Sci Rep. 2019 May 10;9(1):7198. doi: 10.1038/s41598-019-43569-w.
T cells migrate diverse microenvironments of the body to mount antigen-specific immune responses. T cell activation, a key initial process for antigen-specific immune responses, occur in secondary lymphoid organs such as spleens and lymph nodes where high density of T cells migrates rapidly through the reticular networks formed by stromal cells. In vitro model system recapitulating key characteristics of secondary lymphoid organs, confined spaces densely packed with rapidly migrating cells, would be useful to investigate mechanisms of T cell migration. In this study, we devised a method to fabricate microchannels densely packed with T cells. Microchannel arrays with fixed height (4 μm) and length (1.5 mm) and various widths (15~80 μm) were fabricated in between trapezoid-shaped reservoirs that facilitated T cell sedimentation near microchannel entries. Microchannel surface chemistry and filling time were optimized to achieve high packing density (0.89) of T cell filling within microchannels. Particle image velocimetry (PIV) analysis method was employed to extract velocity field of microchannels densely packed with T cells. Using velocity field information, various motility parameters were further evaluated to quantitatively assess the effects of microchannel width and media tonicity on T cell motility within cell dense microenvironments.
T 细胞迁移到身体的各种微环境中,以引发针对抗原的特异性免疫反应。T 细胞激活是针对抗原的特异性免疫反应的关键初始过程,发生在次级淋巴器官中,如脾脏和淋巴结,其中 T 细胞密度高,迅速穿过基质细胞形成的网状结构迁移。体外模型系统重现了次级淋巴器官的关键特征,即充满快速迁移细胞的封闭空间,将有助于研究 T 细胞迁移的机制。在这项研究中,我们设计了一种制造密集排列 T 细胞的微通道的方法。在梯形储液器之间制造了具有固定高度(4 μm)和长度(1.5 mm)以及各种宽度(15~80 μm)的微通道阵列,这有利于 T 细胞在微通道入口附近沉淀。优化了微通道表面化学性质和填充时间,以实现微通道内 T 细胞填充的高填充密度(0.89)。采用粒子图像测速(PIV)分析方法提取密集排列 T 细胞的微通道的速度场。利用速度场信息,进一步评估了各种运动学参数,以定量评估微通道宽度和介质渗透压对细胞密集微环境中 T 细胞运动性的影响。