Biomedical Microdevices

, Volume 10, Issue 4, pp 499–507 | Cite as

Microfluidic switching system for analyzing chemotaxis responses of wortmannin-inhibited HL-60 cells

  • Yuxin Liu
  • Jiqing Sai
  • Ann Richmond
  • John P. Wikswo
Article

Abstract

The chemotaxis of phosphoinositide kinase-3 (PI3K)-inhibited differentiated HL-60 cells stably expressing CXCR2 was studied in a microfluidic switching gradient device that can generate stable and well-defined forward and reverse gradients. Wortmannin, a widely used PI3K inhibitor, was added during cell preparation and the experiment process. The studies quantify the chemotaxis gradient and the effects of a change in the direction of a CXCL-8 gradient on cell migration. PI3K-inhibited HL-60 cells migrated more efficiently toward the gradient before gradient switching than after, as measured by the effective chemotactic index. The inhibited HL-60 cells also showed that inadequate polarization, slower response time, and reduced cell populations can follow the gradient change. We observed that the role of PI3K in directing cellular response to gradient reversal was important in cell polarization and directional sensing associated with gradient switching.

Keywords

Chemotaxis Gradient switching Microfluidic Directional migration HL-60 cells 

References

  1. T.N. Behar, A.E. Schaffner, C.A. Colton, R. Somogyi, Z. Olah, C. Lehel, J.L. Barker, J. Neurosci. 14, 29 (1994)Google Scholar
  2. R. Bird, W. Stewart, E. Lightfoot, Transport Phenomena (Wiley, New York, 1960)Google Scholar
  3. S. Boyden, J. Exper. Med. 115, 453 (1962)CrossRefGoogle Scholar
  4. S.Y. Cheng, S. Heilman, M. Wasserman, S. Archer, M.L. Shuler, M. Wu, Lab Chip 7, 763 (2007)CrossRefGoogle Scholar
  5. S. Dertinger, D. Chiu, N. Jeon, G. Whitesides, Anal. Chem. 73, 1240 (2001)CrossRefGoogle Scholar
  6. B. Gorman, J. Wikswo, Microfluid Nanofluid (in press), DOI 10.1007/s10404-007-0169-0 (2007)
  7. H. Harris, Physiol. Rev. 34, 529 (1954)Google Scholar
  8. E.M. Hersh, G.P. Bodey, Ann. Rev. Med. 21, 105 (1970)CrossRefGoogle Scholar
  9. C. Hsu, A. Folch, Appl. Phys. Lett. 89, 144102 (2006)CrossRefGoogle Scholar
  10. D. Irimia, S. Liu, W.G. Tharp, A. Samadani, M. Toner, M.C. Poznansky, Lab Chip 6, 191 (2006)CrossRefGoogle Scholar
  11. F. Lin, C.M. Nguyen, S. Wang, W. Saadi, S.P. Gross, N.L. Jeon, Biochem. Biophys. Res. Commun. 319, 576 (2004)CrossRefGoogle Scholar
  12. Y.C. Ma, J. Huang, S. Ali, W. Lowry, X.Y. Huang, Cell 102, 635 (2000)CrossRefGoogle Scholar
  13. A.C. Miller, T.R. Thiele, S. Faumont, M.L. Moravec, S.R. Lockery, J. Neurosci. 25, 3369 (2005)CrossRefGoogle Scholar
  14. A. Muller, B. Homey, H. Soto, N. Ge, D. Catron, M.E. Buchanan, T. McClanahan, E. Murphy, W. Yuan, S.N. Wagner, J.L. Barrera, A. Mohar, E. Verastegui, A. Zlotnik, Nature 410, 50 (2001)CrossRefGoogle Scholar
  15. C.A. Parent, B.J. Blacklock, W.M. Froehlich, D.B. Murphy, P.N. Devreotes, Cell 95, 81 (1998)CrossRefGoogle Scholar
  16. A.S. Payne, L.A. Cornelius, J. Invest. Dermatol. 118, 915 (2002)CrossRefGoogle Scholar
  17. T. Sasaki, J. Irie-Sasaki, R.G. Jones, A.J. Oliveira-dos-Santos, W.L. Stanford, B. Bolon, A. Wakeham, A. Itie, D. Bouchard, I. Kozieradzki, N. Joza, T.W. Mak, P.S. Ohashi, A. Suzuki, J.M. Penninger, Science 287, 1040 (2000)CrossRefGoogle Scholar
  18. G. Servant, O.D. Weiner, P. Herzmark, T. Balla, J.W. Sedat, H.R. Bourne, Science 287, 1037 (2000)CrossRefGoogle Scholar
  19. S.M. Thomas, J.S. Brugge, Ann. Rev. Cell. Dev. Biol. 13, 513 (1997)CrossRefGoogle Scholar
  20. M.G. Vicker, Exp. Cell Res. 136, 91 (1981)CrossRefGoogle Scholar
  21. G.M. Walker, J. Sai, A. Richmond, M. Stremler, C.Y. Chung, J.P. Wikswo, Lab Chip 5, 611 (2005)CrossRefGoogle Scholar
  22. F. Wang, P. Herzmark, O.D. Weiner, S. Srinivasan, G. Servant, H.R. Bourne, Nature Cell Biol. 4, 513 (2002)CrossRefGoogle Scholar
  23. D. Zicha, G.A. Dunn, A.F. Brown, J. Cell Sci. 99, 769 (1991)Google Scholar
  24. S.H. Zigmond, J. Cell Biol. 75, 606 (1977)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yuxin Liu
    • 1
  • Jiqing Sai
    • 2
  • Ann Richmond
    • 2
  • John P. Wikswo
    • 1
    • 3
    • 4
  1. 1.Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE), Department of Physics and AstronomyVanderbilt UniversityNashvilleUSA
  2. 2.Department of Veterans Affairs and the Department of Cancer Biology, School of MedicineVanderbilt UniversityNashvilleUSA
  3. 3.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  4. 4.Department of Molecular Physiology and BiophysicsVanderbilt UniversityNashvilleUSA

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