Cell Migration pp 375-386 | Cite as

Microfluidic Devices for Examining the Physical Limits of Migration in Confined Environments

  • Majid Malboubi
  • Asier Jayo
  • Maddy Parsons
  • Guillaume CharrasEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1749)


Cell migration plays a key role in many physiological and pathological conditions during which cells migrate primarily in the 3D environments formed by tissues. Microfluidics enables the design of simple devices that can mimic in a highly controlled manner the geometry and dimensions of the interstices encountered by cells in the body. Here we describe the design, fabrication, and implementation of an array of channels with a range of cross sections to investigate migration of cells and cell clusters through confined spaces. By combining this assay with a motorized microscope stage, image data can be acquired with high throughput to determine the physical limits of migration in confined environments and their biological origin.

Key words

Microfluidics Cell deformation Breast cancer cells Multilayer photolithography 


  1. 1.
    Theveneau E, Mayor R (2012) Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. Dev Biol 366(1):34–54. CrossRefPubMedGoogle Scholar
  2. 2.
    Friedl P, Gilmour D (2009) Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 10(7):445–457. CrossRefPubMedGoogle Scholar
  3. 3.
    Friedl P, Weigelin B (2008) Interstitial leukocyte migration and immune function. Nat Immunol 9(9):960–969. CrossRefPubMedGoogle Scholar
  4. 4.
    Woodfin A, Voisin MB, Nourshargh S (2010) Recent developments and complexities in neutrophil transmigration. Curr Opin Hematol 17(1):9–17. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Friedl P, Alexander S (2011) Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147(5):992–1009. CrossRefPubMedGoogle Scholar
  6. 6.
    Wilson K, Lewalle A, Fritzsche M, Thorogate R, Duke T, Charras G (2013) Mechanisms of leading edge protrusion in interstitial migration. Nat Commun 4:2896. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bergert M, Erzberger A, Desai RA, Aspalter IM, Oates AC, Charras G, Salbreux G, Paluch EK (2015) Force transmission during adhesion-independent migration. Nat Cell Biol 17(4):524–529. CrossRefPubMedGoogle Scholar
  8. 8.
    Ruprecht V, Wieser S, Callan-Jones A, Smutny M, Morita H, Sako K, Barone V, Ritsch-Marte M, Sixt M, Voituriez R, Heisenberg CP (2015) Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. Cell 160(4):673–685. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Liu YJ, Le Berre M, Lautenschlaeger F, Maiuri P, Callan-Jones A, Heuze M, Takaki T, Voituriez R, Piel M (2015) Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. Cell 160(4):659–672. CrossRefPubMedGoogle Scholar
  10. 10.
    Stroka KM, Jiang H, Chen SH, Tong Z, Wirtz D, Sun SX, Konstantopoulos K (2014) Water permeation drives tumor cell migration in confined microenvironments. Cell 157(3):611–623. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Malboubi M, Jayo A, Parsons M, Charras G (2015) An open access microfluidic device for the study of the physical limits of cancer cell deformation during migration in confined environments. Microelectron Eng 144:42–45. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jayo A, Malboubi M, Antoku S, Chang W, Ortiz-Zapater E, Groen C, Pfisterer K, Tootle T, Charras G, Gundersen GG, Parsons M (2016) Fascin regulates nuclear movement and deformation in migrating cells. Dev Cell 38(4):371–383. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kuriyama S, Theveneau E, Benedetto A, Parsons M, Tanaka M, Charras G, Kabla A, Mayor R (2014) In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity. J Cell Biol 206(1):113–127. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Tabeling P (2010) Introduction to microfluidics. Oxford University Press, OxfordGoogle Scholar
  15. 15.
    Folch A (2012) Introduction to BioMEMs. CRC Press, Boca Raton, FLGoogle Scholar
  16. 16.
    Lake M, Narciso C, Cowdrick K, Storey T, Zhang S, Zartman J, Hoelzle D (2015) Microfluidic device design, fabrication, and testing protocols. Protocol Exchange.
  17. 17.
    Millet LJ, Stewart ME, Sweedler JV, Nuzzo RG, Gillette MU (2007) Microfluidic devices for culturing primary mammalian neurons at low densities. Lab Chip 7(8):987–994. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  • Majid Malboubi
    • 1
    • 2
  • Asier Jayo
    • 3
  • Maddy Parsons
    • 4
  • Guillaume Charras
    • 2
    • 5
    • 6
    Email author
  1. 1.Department of Engineering ScienceUniversity of OxfordOxfordUK
  2. 2.London Centre for NanotechnologyUniversity College LondonLondonUK
  3. 3.Universidad CEU San PabloMadridSpain
  4. 4.Randall Division of Cell and Molecular BiophysicsKing’s College LondonLondonUK
  5. 5.Institute for the Physics of Living SystemsUniversity College LondonLondonUK
  6. 6.Department of Cell and Developmental BiologyUniversity College LondonLondonUK

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