Flow-Induced Transport of Tumor Cells in a Microfluidic Capillary Network: Role of Friction and Repeated Deformation



Circulating tumor cells (CTCs) in microcirculation undergo significant deformation and frictional interactions within microcapillaries. To understand the physical parameters governing their flow-induced transport, we studied the pressure-driven flow of cancer cells in a microfluidic model of a capillary network.


Our microfluidic device contains an array of parallel constrictions separated by regions where cells can repetitively deform and relax. To characterize the transport behavior, we measured the entry time, transit time, and shape deformation of tumor cells as they squeeze through the network.


We found that entry and transit times of cells are much lower after repetitive deformation as their elongated shape enables easy transport in subsequent constrictions. Furthermore, upon repetitive deformation, the cells were able to relieve only 25% of their 40% imposed compressional strain, suggesting that tumor cells might have undergone plastic deformation or fatigue. To investigate the influence of surface friction, we characterized the transport behavior in the absence and presence of bovine serum albumin (BSA) coating on the constriction walls. We observed that BSA coating reduces the entry and transit time significantly. Finally, using two breast tumor cell lines, we investigated the effect of metastatic potential on transport properties. We found that the cell lines could be distinguished only upon surface treatment with BSA, thus surface-induced friction is an indicator of metastatic potential.


Our results suggest that pre-deformation can enhance the transport of CTCs in microcirculation and that frictional interactions with capillary walls can play an important role in influencing the transport of metastatic CTCs.

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  1. 1.

    Adamo, A., et al. Microfluidics-based assessment of cell deformability. Anal. Chem. 84:6438–6443, 2012.

    Article  Google Scholar 

  2. 2.

    Bhattacharya, S., A. Datta, J. M. Berg, and S. Gangopadhyay. Studies on surface wettability of poly(dimethyl) siloxane (PDMS) and glass under oxygen-plasma treatment and correlation with bond strength. J. Microelectromech. Syst. 14:590–597, 2005.

    Article  Google Scholar 

  3. 3.

    Byun, S., et al. Characterizing deformability and surface friction of cancer cells. Proc. Natl Acad. Sci. USA 110:7580–7585, 2013.

    Article  Google Scholar 

  4. 4.

    Chambers, A. F., A. C. Groom, and I. C. MacDonald. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2:563–572, 2002.

    Article  Google Scholar 

  5. 5.

    Chang, Y. S., et al. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc. Natl Acad. Sci. USA 97:14608–14613, 2000.

    Article  Google Scholar 

  6. 6.

    Chen, J., et al. Classification of cell types using a microfluidic device for mechanical and electrical measurement on single cells. Lab Chip 11:3174–3181, 2011.

    Article  Google Scholar 

  7. 7.

    Cheng, Y. L., S. A. Darst, and C. R. Robertson. Bovine serum albumin adsorption and desorption rates on solid surfaces with varying surface properties. J. Colloid Interface Sci. 118:212–223, 1987.

    Article  Google Scholar 

  8. 8.

    Das, T., and S. Chakraborty. Perspective: flicking with flow: can microfluidics revolutionize the cancer research? Biomicrofluidics 7:11811, 2013.

    Article  Google Scholar 

  9. 9.

    di Tomaso, E., et al. Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking endothelial cell markers. Cancer Res. 65:5740–5749, 2005.

    Article  Google Scholar 

  10. 10.

    Dobrzynska, I., E. Skrzydlewska, and Z. A. Figaszewski. Changes in electric properties of human breast cancer cells. J. Membr. Biol. 246:161–166, 2013.

    Article  Google Scholar 

  11. 11.

    Friedl, P., and K. Wolf. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat. Rev. Cancer 3:362–374, 2003.

    Article  Google Scholar 

  12. 12.

    Fu, Y., L. K. Chin, T. Bourouina, A. Q. Liu, and A. M. VanDongen. Nuclear deformation during breast cancer cell transmigration. Lab Chip 12:3774–3778, 2012.

    Article  Google Scholar 

  13. 13.

    Gabriele, S., A. M. Benoliel, P. Bongrand, and O. Theodoly. Microfluidic investigation reveals distinct roles for actin cytoskeleton and myosin II activity in capillary leukocyte trafficking. Biophys. J. 96:4308–4318, 2009.

    Article  Google Scholar 

  14. 14.

    Gossett, D. R., et al. Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc. Natl Acad. Sci. USA 109:7630–7635, 2012.

    Article  Google Scholar 

  15. 15.

    Guck, J., et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88:3689–3698, 2005.

    Article  Google Scholar 

  16. 16.

    Guntheroth, W. G., D. L. Luchtel, and I. Kawabori. Pulmonary microcirculation: tubules rather than sheet and post. J. Appl. Physiol. 53:510–515, 1982.

    Google Scholar 

  17. 17.

    Guofeng, G., et al. Real-time control of a microfluidic channel for size-independent deformability cytometry. J. Micromech. Microeng. 22:105037, 2012.

    Article  Google Scholar 

  18. 18.

    Guyton, A. C., and J. E. Hall. Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders, pp. 161–194, 2006.

    Google Scholar 

  19. 19.

    Halldorsson, S., E. Lucumi, R. Gomez-Sjoberg, and R. M. Fleming. Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices. Biosens. Bioelectron. 63:218–231, 2015.

    Article  Google Scholar 

  20. 20.

    Hillborg, H., et al. Crosslinked polydimethylsiloxane exposed to oxygen plasma studied by neutron reflectometry and other surface specific techniques. Polymer 41:6851–6863, 2000.

    Article  Google Scholar 

  21. 21.

    Hou, H. W., et al. Deformability study of breast cancer cells using microfluidics. Biomed. Microdevices 11:557–564, 2009.

    Article  Google Scholar 

  22. 22.

    Kamyabi, N., and S. A. Vanapalli. Microfluidic cell fragmentation for mechanical phenotyping of cancer cells. Biomicrofluidics 10:021102, 2016.

    Article  Google Scholar 

  23. 23.

    Kaneko, N., R. Matsuda, M. Toda, and K. Shimamoto. Three-dimensional reconstruction of the human capillary network and the intramyocardial micronecrosis. Am. J. Physiol. Heart Circ. Physiol. 300:H754–H761, 2011.

    Article  Google Scholar 

  24. 24.

    Khan, Z. S., N. Kamyabi, F. Hussain, and S. A. Vanapalli. Passage times and friction due to flow of confined cancer cells, drops, and deformable particles in a microfluidic channel. Converg. Sci. Phys. Oncol. 3:024001, 2017.

    Article  Google Scholar 

  25. 25.

    Khan, Z. S., and S. A. Vanapalli. Probing the mechanical properties of brain cancer cells using a microfluidic cell squeezer device. Biomicrofluidics 7:11806, 2013.

    Article  Google Scholar 

  26. 26.

    Krebs, M. G., et al. Molecular analysis of circulating tumour cells—biology and biomarkers. Nat. Rev. Clin. Oncol. 11:129–144, 2014.

    Article  Google Scholar 

  27. 27.

    Lange, J. R., et al. Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties. Biophys. J. 109:26–34, 2015.

    Article  Google Scholar 

  28. 28.

    Lee, J. N., X. Jiang, D. Ryan, and G. M. Whitesides. Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane). Langmuir 20:11684–11691, 2004.

    Article  Google Scholar 

  29. 29.

    Mak, M., and D. Erickson. A serial micropipette microfluidic device with applications to cancer cell repeated deformation studies. Integr. Biol. (Camb.) 5:1374–1384, 2013.

    Article  Google Scholar 

  30. 30.

    McDonald, D. M., and P. L. Choyke. Imaging of angiogenesis: from microscope to clinic. Nat. Med. 9:713–725, 2003.

    Article  Google Scholar 

  31. 31.

    Miyamoto, D. T., L. V. Sequist, and R. J. Lee. Circulating tumour cells—monitoring treatment response in prostate cancer. Nat. Rev. Clin. Oncol. 11:401–412, 2014.

    Article  Google Scholar 

  32. 32.

    Ng, J., Y. Shin, and S. Chung. Microfluidic platforms for the study of cancer metastasis. Biomed. Eng. Lett. 2:72–77, 2012.

    Article  Google Scholar 

  33. 33.

    Nguyen, D. X., P. D. Bos, and J. Massague. Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9:274–284, 2009.

    Article  Google Scholar 

  34. 34.

    Nyberg, K. D., et al. The physical origins of transit time measurements for rapid, single cell mechanotyping. Lab Chip 16:3330–3339, 2016.

    Article  Google Scholar 

  35. 35.

    Otto, O., et al. Real-time deformability cytometry: on-the-fly cell mechanical phenotyping. Nat. Methods 12:199–202, 2015.

    Article  Google Scholar 

  36. 36.

    Pantel, K., and M. R. Speicher. The biology of circulating tumor cells. Oncogene 2015. doi:10.1038/onc.2015.

    Google Scholar 

  37. 37.

    Polacheck, W. J., R. Li, S. G. M. Uzel, and R. D. Kamm. Microfluidic platforms for mechanobiology. Lab Chip 13:2252–2267, 2013.

    Article  Google Scholar 

  38. 38.

    Preira, P., M.-P. Valignat, J. Bico, and O. Théodoly. Single cell rheometry with a microfluidic constriction: quantitative control of friction and fluid leaks between cell and channel walls. Biomicrofluidics 7:024111, 2013.

    Article  Google Scholar 

  39. 39.

    Ren, X., P. Ghassemi, H. Babahosseini, J. Strobl, and M. Agah. Single-cell mechanical characteristics analyzed by multi-constriction microfluidic channels. ACS Sens. 2017. doi:10.1021/acssensors.6b00823.

    Google Scholar 

  40. 40.

    Ruths, M., A. D. Berman, and J. N. Israelachvili. In: Nanotribology and Nanomechanics: An Introduction, edited by B. Bhushan. Berlin: Springer, 2005, pp. 389–481.

    Google Scholar 

  41. 41.

    Sakuma, S., et al. Red blood cell fatigue evaluation based on the close-encountering point between extensibility and recoverability. Lab Chip 14:1135–1141, 2014.

    Article  Google Scholar 

  42. 42.

    Schmidt, R. F., and G. Thews (eds.). Human Physiology (2nd ed.). Berlin: Springer, 1989.

    Google Scholar 

  43. 43.

    Schrott, W., et al. Study on surface properties of PDMS microfluidic chips treated with albumin. Biomicrofluidics 3:44101, 2009.

    Article  Google Scholar 

  44. 44.

    Sobin, S. S., H. M. Tremer, and Y. C. Fung. Morphometric basis of the sheet-flow concept of the pulmonary alveolar microcirculation in the cat. Circ. Res. 26:397–414, 1970.

    Article  Google Scholar 

  45. 45.

    Tomaiuolo, G., et al. Microfluidics analysis of red blood cell membrane viscoelasticity. Lab Chip 11:449–454, 2011.

    Article  Google Scholar 

  46. 46.

    Turitto, V. T. Blood viscosity, mass transport, and thrombogenesis. Prog. Hemost. Thromb. 6:139–177, 1982.

    Google Scholar 

  47. 47.

    Vanapalli, S. A., M. H. Duits, and F. Mugele. Microfluidics as a functional tool for cell mechanics. Biomicrofluidics 3:12006, 2009.

    Article  Google Scholar 

  48. 48.

    Weinbaum, S., S. C. Cowin, and Y. Zeng. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27:339–360, 1994.

    Article  Google Scholar 

  49. 49.

    Weinbaum, S., Y. Duan, L. M. Satlin, T. Wang, and A. M. Weinstein. Mechanotransduction in the renal tubule. Am. J. Physiol. Renal Physiol. 299:F1220–F1236, 2010.

    Article  Google Scholar 

  50. 50.

    Williams, S. A., et al. Dynamic measurement of human capillary blood pressure. Clin. Sci. (Lond.) 74:507–512, 1988.

    Article  Google Scholar 

  51. 51.

    Wirtz, D., K. Konstantopoulos, and P. C. Searson. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11:512–522, 2011.

    Article  Google Scholar 

  52. 52.

    Xia, Y., and G. M. Whitesides. Soft lithography. Annu. Rev. Mater. Sci. 28:153–184, 1998.

    Article  Google Scholar 

  53. 53.

    Xue, C., et al. Constriction channel based single-cell mechanical property characterization. Micromachines 6:1457, 2015.

    Google Scholar 

  54. 54.

    Yamauchi, K., et al. Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration. Cancer Res. 65:4246–4252, 2005.

    Article  Google Scholar 

  55. 55.

    Zhang, Z., and S. Nagrath. Microfluidics and cancer: are we there yet? Biomed. Microdevices 15:595–609, 2013.

    Article  Google Scholar 

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We acknowledge support from the Cancer Prevention and Research Institute of Texas (Grant No. RP 140298).

Conflicts of interest

Nabiollah Kamyabi, Zeina S. Khan and Siva A. Vanapalli declare that they have no conflicts of interest.

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No human studies or animal studies were carried out by the authors for this article.

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Correspondence to Siva A. Vanapalli.

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Associate Editor Michael R. King oversaw the review of this article.

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Kamyabi, N., Khan, Z.S. & Vanapalli, S.A. Flow-Induced Transport of Tumor Cells in a Microfluidic Capillary Network: Role of Friction and Repeated Deformation. Cel. Mol. Bioeng. 10, 563–576 (2017). https://doi.org/10.1007/s12195-017-0499-2

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  • Tumor cells
  • Microfluidics
  • Capillary
  • Friction
  • Repeated deformation