Abstract
Biological tissues contain micrometer-scale gaps and pores, including those found within extracellular matrix fiber networks, between tightly packed cells, and between blood vessels or nerve bundles and their associated basement membranes. These spaces restrict cell motion to a single-spatial dimension (1D), a feature that is not captured in traditional in vitro cell migration assays performed on flat, unconfined two-dimensional (2D) substrates. Mechanical confinement can variably influence cell migration behaviors, and it is presently unclear whether the mechanisms used for migration in 2D unconfined environments are relevant in 1D confined environments. Here, we assessed whether a cell migration simulator and associated parameters previously measured for cells on 2D unconfined compliant hydrogels could predict 1D confined cell migration in microfluidic channels. We manufactured microfluidic devices with narrow channels (60-μm2 rectangular cross-sectional area) and tracked human glioma cells that spontaneously migrated within channels. Cell velocities (vexp = 0.51 ± 0.02 μm min−1) were comparable to brain tumor expansion rates measured in the clinic. Using motor-clutch model parameters estimated from cells on unconfined 2D planar hydrogel substrates, simulations predicted similar migration velocities (vsim = 0.37 ± 0.04 μm min−1) and also predicted the effects of drugs targeting the motor-clutch system or cytoskeletal assembly. These results are consistent with glioma cells utilizing a motor-clutch system to migrate in confined environments.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1709-1720 |
| Number of pages | 12 |
| Journal | Biophysical journal |
| Volume | 118 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 7 2020 |
Bibliographical note
Funding Information:We thank the members of the Odde and Piel laboratories for helpful discussions and M. Titus and C. Cadart for comments on the manuscript drafts. We thank R. Attia and M. Fisher for help with photomask design and G. Doak, J. Valdez, X. Lu, and D. Wood for their assistance with photolithography. We thank A. -M. Lennon-Dum?nil for use of laboratory equipment and the Bioimaging Cell and Tissue Core Facility at Institut Curie for use of microscopes during initial data collection. We thank the Minnesota Supercomputing Institute for use of the high-performance computing resources. This work is supported by the National Science Foundation (NSF) through the National Nano Coordinated Infrastructure network under award number ECCS-1542202 (to the Minnesota Nano Center). L.S.P. was supported by a 3M Science & Technology Fellowship and an NSF Graduate Research Fellowship (0039202). M.R.S. was supported by the Undergraduate Research Opportunities Program through the University of Minnesota. Other funding support included an NSF Graduate Research Opportunities Worldwide grant and an STEM Chateaubriand Fellowship to L.S.P. Association Nationale pour la Recherche grant ANR-16-CE13-0009 to P.V. European Research Council consolidator grant 311205 PROMICO to M.P. and National Institutes of Health grants U54 CA210190 and R01 CA172986 to D.J.O. P.V. is an INSERM investigator.
Funding Information:
This work is supported by the National Science Foundation (NSF) through the National Nano Coordinated Infrastructure network under award number ECCS-1542202 (to the Minnesota Nano Center). L.S.P. was supported by a 3M Science & Technology Fellowship and an NSF Graduate Research Fellowship ( 0039202 ). M.R.S. was supported by the Undergraduate Research Opportunities Program through the University of Minnesota . Other funding support included an NSF Graduate Research Opportunities Worldwide grant and an STEM Chateaubriand Fellowship to L.S.P., Association Nationale pour la Recherche grant ANR-16-CE13-0009 to P.V., European Research Council consolidator grant 311205 PROMICO to M.P., and National Institutes of Health grants U54 CA210190 and R01 CA172986 to D.J.O. P.V. is an INSERM investigator.
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