Nano-scale microfluidics to study 3D chemotaxis at the single cell level

被引:27
|
作者
Frick, Corina [1 ,2 ]
Dettinger, Philip [3 ]
Renkawitz, Joerg [4 ]
Jauch, Annaise [1 ,2 ]
Berger, Christoph T. [1 ,2 ]
Recher, Mike [1 ,2 ]
Schroeder, Timm [3 ]
Mehling, Matthias [1 ,2 ,5 ]
机构
[1] Basel Univ, Dept Biomed, Basel, Switzerland
[2] Univ Hosp Basel, Basel, Switzerland
[3] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland
[4] Inst Sci & Technol Austria IST Austria, Klosterneuburg, Austria
[5] Univ Hosp Basel, Dept Neurol Dept, Basel, Switzerland
来源
PLOS ONE | 2018年 / 13卷 / 06期
基金
瑞士国家科学基金会;
关键词
MIGRATION; EXPRESSION; CHEMOKINE; QUANTIFICATION; LYMPHOCYTE; SUBSETS;
D O I
10.1371/journal.pone.0198330
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal-into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controllability of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL1 9 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo.
引用
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页数:17
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