Nanomechanical analysis of cells from cancer patients

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Abstract

Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread1,2. Despite several studies on architectural changes in cultured cell lines1,3, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

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Figure 1: Optical and fluorescence images of a cytological sample.
Figure 2: Histograms of the associated Young's modulus E for cytological samples collected from patients with suspected metastatic cancer.

References

  1. 1

    Bhadriraju, K. & Hansen, L. K. Extracellular matrix- and cytoskeleton-dependent changes in cell shape and stiffness. Exp. Cell Res. 278, 92–100 (2002).

  2. 2

    Discher, D., Janmey, P. & Wang, Y. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).

  3. 3

    Radmacher, M. Measuring the elastic properties of biological samples with the AFM. IEEE Eng. Med. Biol. Mag. 16, 47–57 (1997).

  4. 4

    Yamazaki, D., Kurisu, S. & Takenawa, T. Regulation of cancer cell motility through actin reorganization. Cancer Sci. 96, 379–386 (2005).

  5. 5

    Rao, J. & Li, N. Microfilament actin remodeling as a potential target for cancer drug development. Curr. Cancer Drug Targ. 4, 267–283 (2004).

  6. 6

    Motherby, H. et al. Pleural carcinosis confirmed by adjuvant cytological methods: A case report. Diag. Cytopathol. 19, 370–374 (1998).

  7. 7

    Osterheld, M., Liette, C. & Anca, M. M. D. Image cytometry: an aid for cytological diagnosis of pleural effusions. Diag. Cytopathol. 32, 173–176 (2005).

  8. 8

    McKnight, A. L. et al. MR elastography of breast cancer: preliminary results. AJR Am. J. Roentgenol. 178, 1411–1417 (2002).

  9. 9

    Bercoff, J. et al. In vivo breast tumor detection using transient elastography. Ultrasound Med. Biol. 29, 1387–1396 (2003).

  10. 10

    Rotsch, C. & Radmacher, M. Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys. J. 78, 520–535 (2000).

  11. 11

    Lee, J., Ishihara, A. & Jacobson, K. How do cells move along surfaces? Trends Cell Biol. 3, 366–370 (1993).

  12. 12

    Stossel, T. P. On the crawling of animal cells. Science 260, 1086–1094 (1993).

  13. 13

    Suresh, S. et al. Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomaterialia 1, 15–30 (2005).

  14. 14

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

  15. 15

    Suresh, S. Biomechanics and biophysics of cancer cell. Acta Biomaterialia 3, 413–438 (2007).

  16. 16

    Binnig, G., Quate, C. & Gerber, C. Atomic force microscope. Phys. Rev. Lett. 56, 930–933 (1986).

  17. 17

    Rotsch, C., Braet, F., Wisse, E. & Radmacher, M. AFM imaging and elasticity measurements on living rat liver macrophages. Cell Biol. Int. 21, 685–696 (1997).

  18. 18

    Charras, G. T. & Horton, M. A. Single cell mechanotransduction and its modulation analyzed by atomic force microscopy indentation. Biophys. J. 82, 2970–2981 (2002).

  19. 19

    Dufrene, Y. F. Atomic force microscopy, a powerful tool in microbiology. J. Bacteriol. 184, 5205–5213 (2002).

  20. 20

    Pelling, A. E., Li, Y., Shi, W. & Gimzewski, J. K. Nanoscale visualization and characterization of Myxococcus xanthus cells with atomic force microscopy. Proc. Natl Acad. Sci. USA 102, 6484–6489 (2005).

  21. 21

    Pelling, A. E., Sehati, S., Gralla, E. B., Valentine, J. S. & Gimzewski, J. K. Local nanomechanical motion of the cell wall of Saccharomyces cerevisiae. Science 305, 1147–1150 (2004).

  22. 22

    Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J. M. & Gaub, H. E. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276, 1109–1112 (1997).

  23. 23

    Kasas, S., Gotzos, V. & Celio, M. R. Observation of living cells using the atomic force microscope. Biophys. J. 64, 539–544 (1993).

  24. 24

    Hansma, P. K. et al. Tapping mode atomic force microscopy in liquids. Appl. Phys. Lett. 64, 1738–1740 (1994).

  25. 25

    Salgia, R. et al. Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility. Oncogene 18, 67–77 (1999).

  26. 26

    Wu, H. W., Kuhn, T. & Moy, V. T. Mechanical properties of 1929 cells measured by atomic force microscopy: effects of anticytoskeletal drugs and membrane crosslinking. Scanning 20, 389–397 (1998).

  27. 27

    Levy, R. & Maaloum, M. Measuring the spring constant of atomic force microscope cantilevers: thermal fluctuations and other methods. Nanotechnology 13, 33–37 (2002).

  28. 28

    Touhami, A., Nysten, B. & Dufrene, Y. F. Nanoscale mapping of the elasticity of microbial cells by atomic force microscopy. Langmuir 19, 4539–4543 (2003).

  29. 29

    Matzke, R., Jacobson, K. & Radmacher, M. Direct, high-resolution measurement of furrow stiffening during division of adherent cells. Nature Cell Biol. 3, 607–610 (2001).

  30. 30

    Stolz, M. et al. Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. Biophys. J. 86, 3269–3283 (2004).

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Acknowledgements

S.E.C. and J.K.G. acknowledge partial support from National Institutes of Health research grant no. 5 R21 GM074509 and from the Institute for Cell Mimetic Space Exploration, a National Aeronautics and Space Administration University Research Engineering Technology Institute. J.R. and Y.J. acknowledge partial support from National Institutes of Health research grant no. U01CA96116 and Alper grant, Johnsson Comprehensive Cancer Center.

Author information

S.E.C., Y.J., J.R. and J.K.G. contributed equally to this work.

Correspondence to Jianyu Rao or James K. Gimzewski.

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Supplementary Information

Supplementary discussion, supplementary table S1 and supplementary figure S1 (PDF 2437 kb)

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Cross, S., Jin, Y., Rao, J. et al. Nanomechanical analysis of cells from cancer patients. Nature Nanotech 2, 780–783 (2007) doi:10.1038/nnano.2007.388

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