Frick, Corina; Dettinger, Philip; Renkawitz, JoergIST Austria; Jauch, Annaïse; Berger, Christoph; Recher, Mike; Schroeder, Timm; Mehling, Matthias
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 controlla-bility 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 CCL19 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.
This work was supported by the Swiss National Science Foundation (MD-PhD fellowships, 323530_164221 to C.F.; and 323630_151483 to A.J.; grant PZ00P3_144863 to M.R, grant 31003A_156431 to T.S.; PZ00P3_148000 to C.T.B.; PZ00P3_154733 to M.M.), a Novartis “FreeNovation” grant to M.M. and T.S. and an EMBO long-term fellowship (ALTF 1396-2014) co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409) to J.R.. M.R. was supported by the Gebert Rüf Foundation (GRS 058/14). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Frick C, Dettinger P, Renkawitz J, et al. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 2018;13(6). doi:10.1371/journal.pone.0198330
Frick, C., Dettinger, P., Renkawitz, J., Jauch, A., Berger, C., Recher, M., … Mehling, M. (2018). Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One, 13(6). https://doi.org/10.1371/journal.pone.0198330
Frick, Corina, Philip Dettinger, Jörg Renkawitz, Annaïse Jauch, Christoph Berger, Mike Recher, Timm Schroeder, and Matthias Mehling. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One 13, no. 6 (2018). https://doi.org/10.1371/journal.pone.0198330.
C. Frick et al., “Nano-scale microfluidics to study 3D chemotaxis at the single cell level,” PLoS One, vol. 13, no. 6, 2018.
Frick C, Dettinger P, Renkawitz J, Jauch A, Berger C, Recher M, Schroeder T, Mehling M. 2018. Nano-scale microfluidics to study 3D chemotaxis at the single cell level. PLoS One. 13(6).
Frick, Corina, et al. “Nano-Scale Microfluidics to Study 3D Chemotaxis at the Single Cell Level.” PLoS One, vol. 13, no. 6, e0198330, Public Library of Science, 2018, doi:10.1371/journal.pone.0198330.
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