Skip to main content
SpringerLink
Log in

Atomic force microscopy studies on cellular elastic and viscoelastic properties

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

In this work, a method based on atomic force microscopy (AFM) approach-reside-retract experiments was established to simultaneously quantify the elastic and viscoelastic properties of single cells. First, the elastic and viscoelastic properties of normal breast cells and cancerous breast cells were measured, showing significant differences in Young’s modulus and relaxation times between normal and cancerous breast cells. Remarkable differences in cellular topography between normal and cancerous breast cells were also revealed by AFM imaging. Next, the elastic and viscoelasitc properties of three other types of cell lines and primary normal B lymphocytes were measured; results demonstrated the potential of cellular viscoelastic properties in complementing cellular Young’s modulus for discerning different states of cells. This research provides a novel way to quantify the mechanical properties of cells by AFM, which allows investigation of the biomechanical behaviors of single cells from multiple aspects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baskar, S., Kwong, K.Y., Hofer, T., Levy, J.M., Kennedy, M.G., Lee, E., Staudt, L.M., Wilson, W.H., Wiestner, A., and Rader, C. (2008). Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-Cell chronic lymphocytic leukemia. Clin Cancer Res 14, 396–404.

    Article  CAS  PubMed  Google Scholar 

  • Bicocca, V.T., Chang, B.H., Masouleh, B.K., Muschen, M., Loriaux, M.M., Druker, B.J., and Tyner, J.W. (2012). Crosstalk between ROR1 and the pre-B cell receptor promotes survival of t(1;19) acute lymphoblastic leukemia. Cancer Cell 22, 656–667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canetta, E., Riches, A., Borger, E., Herrington, S., Dholakia, K., and Adya, A.K. (2014). Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy. Acta Biomater 10, 2043–2055.

    Article  CAS  PubMed  Google Scholar 

  • Cross, S.E., Jin, Y.S., Rao, J., and Gimzewski, J.K. (2007). Nanomechanical analysis of cells from cancer patients. Nat Nanotech 2, 780–783.

    Article  CAS  Google Scholar 

  • Darbre, P.D., Bakir, A., and Iskakova, E. (2013). Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture. J Inorg Biochem 128, 245–249.

    Article  CAS  PubMed  Google Scholar 

  • Di Carlo, D. (2012). A mechanical biomarker of cell state in medicine. J Lab Autom 17, 32–42.

    Article  PubMed  Google Scholar 

  • Dufrêne, Y.F., Martínez-Martín, D., Medalsy, I., Alsteens, D., and Müller, D.J. (2013). Multiparametric imaging of biological systems by forcedistance curve-based AFM. Nat Meth 10, 847–854.

    Article  Google Scholar 

  • Eghiaian, F., Rigato, A., and Scheuring, S. (2015). Structural, mechanical, and dynamical variability of the actin cortex in living cells. Biophys J 108, 1330–1340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan, D., and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646–674.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi, K., and Iwata, M. (2015). Stiffness of cancer cells measured with an AFM indentation method. J Mech Behav Biomed Mater 49, 105–111.

    Article  PubMed  Google Scholar 

  • Hecht, F.M., Rheinlaender, J., Schierbaum, N., Goldmann, W.H., Fabry, B., and Schäffer, T.E. (2015). Imaging viscoelastic properties of live cells by AFM: power-law rheology on the nanoscale. Soft Matter 11, 4584–4591.

    Article  CAS  PubMed  Google Scholar 

  • Hu, S., Liu, G., Chen, W., Li, X., Lu, W., Lam, R.H.W., and Fu, J. (2016). Multiparametric biomechanical and biochemical phenotypic profiling of single cancer cells using an elasticity microcytometer. Small 12, 2300–2311.

    Article  CAS  PubMed  Google Scholar 

  • Huang, T., Jia, C.P., Jun-Yang, C.P., Sun, W.J., Wang, W.T., Zhang, H.L., Cong, H., Jing, F.X., Mao, H.J., Jin, Q.H., Zhang, Z., Chen, Y.J., Li, G., Mao, G.X., and Zhao, J.L. (2014). Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. Biosens Bioelectron 51, 213–218.

    Article  CAS  PubMed  Google Scholar 

  • Hutter, J.L., and Bechhoefer, J. (1993). Calibration of atomic-force microscope tips. Rev Sci Instrum 64, 1868–1873.

    Article  CAS  Google Scholar 

  • Iyer, S., Gaikwad, R.M., Subba-Rao, V., Woodworth, C.D., and Sokolov, I. (2009). Atomic force microscopy detects differences in the surface brush of normal and cancerous cells. Nat Nanotech 4, 389–393.

    Article  CAS  Google Scholar 

  • Junttila, M.R., and de Sauvage, F.J. (2013). Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346–354.

    Article  CAS  PubMed  Google Scholar 

  • Kasas, S., Longo, G., and Dietler, G. (2013). Mechanical properties of biological specimens explored by atomic force microscopy. J Phys D Appl Phys 46, 133001.

    Article  Google Scholar 

  • Keren, K., Pincus, Z., Allen, G.M., Barnhart, E.L., Marriott, G., Mogilner, A., and Theriot, J.A. (2008). Mechanism of shape determination in motile cells. Nature 453, 475–480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ketene, A.N., Roberts, P.C., Shea, A.A., Schmelz, E.M., and Agah, M. (2012). Actin filaments play a primary role for structural integrity and viscoelastic response in cells. Integr Biol 4, 540–549.

    Article  CAS  Google Scholar 

  • Kiberstis, P.A. (2016). Metastasis: an evolving story. Science 352, 162–163.

    Article  CAS  PubMed  Google Scholar 

  • Kirmizis, D., and Logothetidis, S. (2010). Atomic force microscopy probing in the measurement of cell mechanics. Int J Nanomed 5, 137–145.

    Article  Google Scholar 

  • Kliche, K., Jeggle, P., Pavenstädt, H., and Oberleithner, H. (2011). Role of cellular mechanics in the function and life span of vascular endothelium. Eur J Physiol 462, 209–217.

    Article  CAS  Google Scholar 

  • Kuznetsova, T.G., Starodubtseva, M.N., Yegorenkov, N.I., Chizhik, S.A., and Zhdanov, R.I. (2007). Atomic force microscopy probing of cell elasticity. Micron 38, 824–833.

    Article  CAS  PubMed  Google Scholar 

  • Lekka, M. (2016). Discrimination between normal and cancerous cells using AFM. Bionanoscience 6, 65–80.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lekka, M., Gil, D., Pogoda, K., Dulińska-Litewka, J., Jach, R., Gostek, J., Klymenko, O., Prauzner-Bechcicki, S., Stachura, Z., Wiltowska-Zuber, J., Okoń, K., and Laidler, P. (2012). Cancer cell detection in tissue sections using AFM. Arch Biochem Biophys 518, 151–156.

    Article  CAS  PubMed  Google Scholar 

  • Lekka, M., Pogoda, K., Gostek, J., Klymenko, O., Prauzner-Bechcicki, S., Wiltowska-Zuber, J., Jaczewska, J., Lekki, J., and Stachura, Z. (2012). Cancer cell recognition—mechanical phenotype. Micron 43, 1259–1266.

    Article  PubMed  Google Scholar 

  • Li, M., Liu, L.Q., Xi, N., Wang, Y.C., Dong, Z.L., Xiao, X.B., and Zhang, W.J. (2012). Atomic force microscopy imaging and mechanical properties measurement of red blood cells and aggressive cancer cells. Sci China Life Sci 55, 968–973.

    Article  PubMed  Google Scholar 

  • Li, M., Liu, L., Xiao, X., Xi, N., and Wang, Y. (2016a). Viscoelastic properties measurement of human lymphocytes by atomic force microscopy based on magnetic beads cell isolation. IEEE Trans Nanobiosci 15, 398–411.

    Article  Google Scholar 

  • Li, M., Liu, L.Q., Xi, N., Wang, Y.C., Xiao, X.B., and Zhang, W.J. (2015). Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy. Sci China Life Sci 58, 889–901.

    Article  CAS  PubMed  Google Scholar 

  • Li, M., Liu, L., Xiao, X., Xi, N., and Wang, Y. (2016b). Effects of methotrexate on the viscoelastic properties of single cells probed by atomic force microscopy. J Biol Phys 42, 551–569.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, M., Liu, L., Xi, N., Wang, Y., Xiao, X., and Zhang, W. (2014a). Nanoscale imaging and mechanical analysis of fc receptor-mediated macrophage phagocytosis against cancer cells. Langmuir 30, 1609–1621.

    Article  CAS  PubMed  Google Scholar 

  • Li, M., Xiao, X., Zhang, W., Liu, L., Xi, N., and Wang, Y. (2014b). AFM analysis of the multiple types of molecular interactions involved in rituximab lymphoma therapy on patient tumor cells and NK cells. Cell Immunol 290, 233–244.

    Article  CAS  PubMed  Google Scholar 

  • Li, Q.S., Lee, G.Y.H., Ong, C.N., and Lim, C.T. (2008). AFM indentation study of breast cancer cells. Biochem Biophys Res Commun 374, 609–613.

    Article  CAS  PubMed  Google Scholar 

  • Liang, X., Shi, X., Ostrovidov, S., Wu, H., and Nakajima, K. (2016). Probing stem cell differentiation using atomic force microscopy. Appl Surf Sci 366, 254–259.

    Article  CAS  Google Scholar 

  • Matthews, H.K., Delabre, U., Rohn, J.L., Guck, J., Kunda, P., and Baum, B. (2012). Changes in ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression. Dev Cell 23, 371–383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medalsy, I.D., and Müller, D.J. (2013). Nanomechanical properties of proteins and membranes depend on loading rate and electrostatic interactions. ACS Nano 7, 2642–2650.

    Article  CAS  PubMed  Google Scholar 

  • Moeendarbary, E., Valon, L., Fritzsche, M., Harris, A.R., Moulding, D.A., Thrasher, A.J., Stride, E., Mahadevan, L., and Charras, G.T. (2013). The cytoplasm of living cells behaves as a poroelastic material. Nat Mater 12, 253–261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno-Flores, S., Benitez, R., Vivanco, M.D., and Toca-Herrera, J.L. (2010). Stress relaxation microscopy: imaging local stress in cells. J Biomech 43, 349–354.

    Article  PubMed  Google Scholar 

  • Nijenhuis, N., Zhao, X., Carisey, A., Ballestrem, C., and Derby, B. (2014). Combining AFM and acoustic probes to reveal changes in the elastic stiffness tensor of living cells. Biophys J 107, 1502–1512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okajima, T., Tanaka, M., Tsukiyama, S., Kadowaki, T., Yamamoto, S., Shimomura, M., and Tokumoto, H. (2007). Stress relaxation of HepG2 cells measured by atomic force microscopy. Nanotechnology 18, 084010.

    Article  Google Scholar 

  • Park, S., and Lee, Y.J. (2014). AFM-based dual nano-mechanical phenotypes for cancer metastasis. J Biol Phys 40, 413–419.

    Article  PubMed  PubMed Central  Google Scholar 

  • Plessner, M., Melak, M., Chinchilla, P., Baarlink, C., and Grosse, R. (2015). Nuclear F-actin formation and reorganization upon cell spreading. J Biol Chem 290, 11209–11216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plodinec, M., Loparic, M., Monnier, C.A., Obermann, E.C., Zanetti-Dallenbach, R., Oertle, P., Hyotyla, J.T., Aebi, U., Bentires-Alj, M., Lim, R.Y.H., and Schoenenberger, C.A. (2012). The nanomechanical signature of breast cancer. Nat Nanotech 7, 757–765.

    Article  CAS  Google Scholar 

  • Reich, A., Meurer, M., Eckes, B., Friedrichs, J., and Muller, D.J. (2009). Surface morphology and mechanical properties of fibroblasts from scleroderma patients. J Cell Mol Med 13, 1644–1652.

    Article  PubMed  Google Scholar 

  • Rianna, C., Ventre, M., Cavalli, S., Radmacher, M., and Netti, P.A. (2015). Micropatterned azopolymer surfaces modulate cell mechanics and cytoskeleton structure. ACS Appl Mater Interfaces 7, 21503–21510.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schillers, H., Medalsy, I., Hu, S., Slade, A.L., and Shaw, J.E. (2016). Peakforce tapping resolves individual microvilli on living cells. J Mol Recognit 29, 95–101.

    Article  CAS  PubMed  Google Scholar 

  • Simon, M., Dokukin, M., Kalaparthi, V., Spedden, E., Sokolov, I., and Staii, C. (2016). Load rate and temperature dependent mechanical properties of the cortical neuron and its pericellular layer measured by atomic force microscopy. Langmuir 32, 1111–1119.

    Article  CAS  PubMed  Google Scholar 

  • Suresh, S. (2007a). Biomechanics and biophysics of cancer cells. Acta Biomater 3, 413–438.

    Article  PubMed  PubMed Central  Google Scholar 

  • Suresh, S. (2007b). Nanomedicine: elastic clues in cancer detection. Nat Nanotech 2, 748–749.

    Article  CAS  Google Scholar 

  • Ursell, T.S., Nguyen, J., Monds, R.D., Colavin, A., Billings, G., Ouzounov, N., Gitai, Z., Shaevitz, J.W., and Huang, K.C. (2014). Rod-like bacterial shape is maintained by feedback between cell curvature and cytoskeletal localization. Proc Natl Acad Sci USA 111, E1025–E1034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vargas-Pinto, R., Gong, H., Vahabikashi, A., and Johnson, M. (2013). The effect of the endothelial cell cortex on atomic force microscopy measurements. Biophys J 105, 300–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, H., Mouw, J.K., and Weaver, V.M. (2011). Forcing form and function: biomechanical regulation of tumor evolution. Trends Cell Biol 21, 47–56.

    Article  PubMed  Google Scholar 

  • Zheng, Y., Nguyen, J., Wei, Y., and Sun, Y. (2013). Recent advances in microfluidic techniques for single-cell biophysical characterization. Lab Chip 13, 2464–2483.

    Article  CAS  PubMed  Google Scholar 

  • Zhou, E.H., Martinez, F.D., and Fredberg, J.J. (2013). Cell rheology: mush rather than machine. Nat Mater 12, 184–185.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (61503372, 61522312, U1613220, 61327014, 61433017), the Youth Innovation Promotion Association CAS (2017243), and the CAS FEA International Partnership Program for Creative Research Teams.

Author information

Authors and Affiliations

  1. State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, 110016, China

    Mi Li, Lianqing Liu, Ning Xi & Yuechao Wang

  2. Department of Industrial and Manufacturing Systems Engineering, The University of Hong Kong, Hong Kong, China

    Ning Xi

Authors
  1. Mi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lianqing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ning Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuechao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lianqing Liu or Ning Xi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, M., Liu, L., Xi, N. et al. Atomic force microscopy studies on cellular elastic and viscoelastic properties. Sci. China Life Sci. 61, 57–67 (2018). https://doi.org/10.1007/s11427-016-9041-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-016-9041-9

Keywords

Search

Navigation