Abstract
Cell migration under chemoattractant is an important biological step in cancer metastasis that causes the spread of malignant tumor cells. Porous polymeric materials are widely used to mimic the extracellular matrix (ECM) environment for applications such as three dimensional (3D) cell culturing and tissue engineering. In this paper we report a novel 3D cell culture device based on porous polymeric material to study cancer migration. We fabricated a porous channel on a polymeric chip using a selective ultrasonic foaming method. We demonstrate that a chemical concentration gradient could be established through the porous channel due to the slow diffusion process. We show that significant cell migration could be observed through the porous channel within 1–2 weeks of cell culturing when metastatic M4A4-GFP breast cancer cells were induced by 20% fetal bovine serum (FBS).We also developed a mathematical model to evaluate the diffusivity and concentration gradient through the fabricated porous structure.
Similar content being viewed by others
References
Z.N. Al-Sokanee, A.A. Toabi, M.J. Al-Assadi, E.A. Alassadi, The drug release study of ceftriaxone from porous hydroxyapatite scaffolds. AAPS PharmSciTech (2009)
S. Boyden, The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. The Journal of Experimental Medicine 115, 453–466 (1962)
W.J. Brackenbury, M.B. Djamgoz, Nerve growth factor enhances voltage-gated Na+ channel activity and transwell migration in Mat-LyLu rat prostate cancer cell line. Journal of Cellular Physiology 210, 602–608 (2007)
A.F. Chambers, A.C. Groom, I.C. MacDonald, Dissemination and growth of cancer cells in metastatic sites. Nature Reviews. Cancer 2, 563–572 (2002)
K.C. Chaw, M. Manimaran, F.E. Tay, S. Swaminathan, A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel. Microvascular Research 72, 153–160 (2006)
K.C. Chaw, M. Manimaran, F.E. Tay, S. Swaminathan, Matrigel coated polydimethylsiloxane based microfluidic devices for studying metastatic and non-metastatic cancer cell invasion and migration. Biomedical Microdevices 9, 597–602 (2007)
S.H. Cho, S.H. Oh, J.H. Lee, Fabrication and characterization of porous alginate/polyvinyl alcohol hybrid scaffolds for 3D cell culture. Journal of Biomaterials Science, Polymer Edition 16, 933–947 (2005)
J.G. Christie, Transport Processes and Separation Process Principles, 4th edn. (Prentice Hall, 2003)
C. Decaestecker, O. Debeir, P. Van Ham, R. Kiss, Can anti-migratory drugs be screened in vitro? A review of 2D and 3D assays for the quantitative analysis of cell migration. Medicinal Research Reviews 27, 149–176 (2007)
J. Diao, L. Young, S. Kim, E.A. Fogarty, S.M. Heilman, P. Zhou, M.L. Shuler, M. Wu, M.P. DeLisa, A three-channel microfluidic device for generating static linear gradients and its application to the quantitative analysis of bacterial chemotaxis. Lab on a Chip 6, 381–388 (2006)
S. Even-Ram, K.M. Yamada, Cell migration in 3D matrix. Current Opinion in Cell Biology 17, 524–532 (2005)
A. Fardet, C. Hoebler, G. Djelveh, J.-L. Barry, Restricted bovine serum albumin diffusion through the protein network of pasta. Journal of Agricultural and Food Chemistry 46, 4635–4641 (1998)
H. Huang, S. Oizumi, N. Kojima, T. Niino, Y. Sakai, Avidin-biotin binding-based cell seeding and perfusion culture of liver-derived cells in a porous scaffold with a three-dimensional interconnected flow-channel network. Biomaterials 28, 3815–3823 (2007)
D.A. Lauffenburger, A.F. Horwitz, Cell migration: a physically integrated molecular process. Cell 84, 359–369 (1996)
S.H. Lee, J.J. Moon, J.L. West, Three-dimensional micropatterning of bioactive hydrogels via two-photon laser scanning photolithography for guided 3D cell migration. Biomaterials 29, 2962–2968 (2008)
Z. Li, J. Gunn, M.H. Chen, A. Cooper, M. Zhang, On-site alginate gelation for enhanced cell proliferation and uniform distribution in porous scaffolds. Journal of Biomedical Materials Research. Part A 86, 552–559 (2008)
Y.J. Lin, C.N. Yen, Y.C. Hu, Y.C. Wu, C.J. Liao, I.M. Chu, Chondrocytes culture in three-dimensional porous alginate scaffolds enhanced cell proliferation, matrix synthesis and gene expression. Journal of Biomedical Materials Research. Part A 88, 23–33 (2009)
B. Niggemann, T.L. Drell IV, J. Joseph, C. Weidt, K. Lang, K.S. Zaenker, F. Entschladen, Tumor cell locomotion: differential dynamics of spontaneous and induced migration in a 3D collagen matrix. Experimental Cell Research 298, 178–187 (2004)
Polson, The some aspects of diffusion in solution and a definition of a colloidal particle. J. Phys. Colloid Chem 54, (1950)
P.D. Ponath, J. Wang, H. Heath, Transwell chemotaxis. Methods in Molecular Biology 138, 113–120 (2000)
E. Ruoslahti, How cancer spreads. Scientific American 275, 72–77 (1996)
B. Ruster, B. Grace, O. Seitz, E. Seifried, R. Henschler, Induction and detection of human mesenchymal stem cell migration in the 48-well reusable transwell assay. Stem Cells and Development 14, 231–235 (2005)
C.N. Satterfield, Mass Transfer in Heterogeneous Catalysis (MIT, Cambridge, 1970)
M. Uttarwar, P. Aswath, Fabrication of porous, drug-releasing, biodegradable, polymer scaffolds for sustained drug release. Journal of Biomedical Materials Research. Part B: Applied Biomaterials 87, 121–131 (2008)
H. Wang, W Li, A novel passive polymeric micromixer fabricated using selective ultrasonic foaming. Journal of Micromechanics and Microengineering 17, 1835–1842 (2007)
H. Wang, W. Li, Selective ultrasonic foaming of polymer for biomedical applications. ASME Transaction Journal of Manufacturing Science and Engineering 130(2), 021004-1–021004–9 (2008)
S.E. Webb, J.W. Pollard, G.E. Jones, Direct observation and quantification of macrophage chemoattraction to the growth factor CSF-1. Journal of Cell Science 109(Pt 4), 793–803 (1996)
D. Zicha, G. Dunn, G. Jones, Analyzing chemotaxis using the Dunn direct-viewing chamber. Methods in Molecular Biology 75, 449–457 (1997)
Acknowledgements
This research was partially supported through grants from NIH (5R21EB008573) and NSF (CMMI0348767). We acknowledge Mr. Nicholas Vaccaro for help in SEM imaging and Mr. Zhe Xu for help in machining. SEM and confocal images were taken at University of Washington Nanotechnology User Facility Center.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ma, L., Zhou, C., Lin, B. et al. A porous 3D cell culture micro device for cell migration study. Biomed Microdevices 12, 753–760 (2010). https://doi.org/10.1007/s10544-010-9429-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-010-9429-y