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Nanomechanical analysis of cells from cancer patients


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.


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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

  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).

    CAS  Article  Google Scholar 

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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.

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

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Correspondence to Jianyu Rao or James K. Gimzewski.

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

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Cross, S., Jin, YS., Rao, J. et al. Nanomechanical analysis of cells from cancer patients. Nature Nanotech 2, 780–783 (2007).

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