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Investigation of effect of fullerenol on viscoelasticity properties of human hepatocellular carcinoma by AFM-based creep tests

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Abstract

Cellular elasticity is frequently measured to investigate the biomechanical effects of drug treatment, diseases, and aging. In light of the cellular viscosity property exhibited by filament actin networks, this study investigates the viscoelasticity alterations of the human hepatocellular carcinoma (SMMC-7721) cell subjected to fullerenol treatment by means of creep tests realized by atomic force microscopy indentation. An SMMC-7721 cell was first modeled as a sphere and then as a flattened layer with finite thickness. Both Sneddon’s solutions and the Dimitriadis model have been modified to adapt to the viscoelastic situation, which are used to fit the same indentation depth–time curves obtained by creep tests. We find that the SMMC-7721 cell’s creep behavior is well described by the two modified models and the divergence of parameters determined by the two models is justified. By fullerenol treatment, the SMMC-7721 cell exhibits a significant decrease of elastic modulus and viscosity, which is presumably due to the disruption of actin filaments. This work represents a new attempt to understand the alternation of the viscoelastic properties of cancerous cells under the treatment of fullerenol, which has the significance of comprehensively elucidating the biomechanical effects of anticancer agents (such as fullerenol) on cancer cells.

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References

  1. Z. Chen, L. Ma, Y. Liu, and C. Chen: Applications of functionalized fullerenes in tumor theranostics. Theranostics 2, 238 (2012).

    Article  CAS  Google Scholar 

  2. R. Partha and J.L. Conyers: Biomedical applications of functionalized fullerene-based nanomaterials. Int. J. Nanomed. 4, 261 (2009).

    Article  CAS  Google Scholar 

  3. S. Bosi, R.T. Da, G. Spalluto, and M. Prato: Fullerene derivatives: An attractive tool for biological applications. Eur. J. Med. Chem. 38, 913 (2003).

    Article  CAS  Google Scholar 

  4. J. Li, A. Takeuchi, M. Ozawa, X.H. Li, K. Saigo, and K. Kitazawa: C-60 fullerol formation catalyzed by quaternary ammonium hydroxides. J. Chem. Soc., Chem. Commun. 23, 1784 (1993).

    Article  Google Scholar 

  5. J. Jin, Y. Dong, Y. Wang, L. Xia, and W. Gu: Fullerenol Nanoparticles with structural activity induce variable intracellular actin filament morphologies. J. Biomed. Nanotechnol. 12, 1234 (2016).

    Article  CAS  Google Scholar 

  6. Y.T. Zhou, G.R. Guy, and B.C. Low: BNIP-Sa induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain. Oncogene 25, 2393 (2006).

    Article  CAS  Google Scholar 

  7. D.N. Johnson-Lyles, K. Peifley, S. Lockett, B.W. Neun, M. Hansen, J. Clogston, S.T. Stern, and S.E. McNeil: Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction. Toxicol. Appl. Pharmacol. 248, 249 (2010).

    Article  CAS  Google Scholar 

  8. J.D. Zhu, Z.Q. Ji, J. W, R.H. Sun, X. Zhang, Y. Gao, H. Sun, Y. Liu, Z. Wang, A. Li, J. Ma, T. Wang, G. Jia, and Y. Gu: Tumor-inhibitory effect and immunomodulatory activity of fullerol C60(OH)x. Small. 4, 1168 (2008).

    Article  CAS  Google Scholar 

  9. L.H. Lu, Y.T. Lee, H.W. Chen, Y.C. Long, and H.C. Huang: The possible mechanisms of the antiproliferative effect of fullerenol, polyhydroxylated C60, on vascular smooth muscle cells. Br. J. Pharmacol. 123, 1097 (1998).

    Article  CAS  Google Scholar 

  10. A. Paraskar, S. Soni, R.A. Mashelkar, and S. Sengupta: Fullerenol–cytotoxic conjugates for cancer chemotherapy. ACS Nano 3, 2505 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. T. Hawkins, M. Mirigian, M.S. Yasar, and J.L. Ross: Mechanics of microtubules. J. Biomech. 43, 23 (2010).

    Article  Google Scholar 

  13. J. Mrdanović, S. Solajić, V. Bogdanović, K. Stankov, G. Bogdanovicć, and A. Djordjevic: Effects of fullerenol C60(OH)24 on the frequency of micronuclei and chromosome aberrations in CHO-K1 cells. Mutat. Res., Genet. Toxicol. Environ. Mutagen. 680, 25 (1999).

    Article  CAS  Google Scholar 

  14. E. Siamantouras, C.E. Hills, M.Y. Younis, P.E. Squire, and K.K. Liu: Quantitative investigation of calcimimetic R568 on beta cell adhesion and mechanics using AFM single-cell force spectroscopy. FEBS Lett. 588, 1178 (2014).

    Article  CAS  Google Scholar 

  15. G. Thomas, N.A. Burnham, T.A. Camesano, and Q. Wen: Measuring the mechanical properties of living cells using atomic force microscopy. J. Visualized Exp. 76, e50497 (2013).

    Google Scholar 

  16. C. Rianna and M. Radmacher: Cell mechanics as a marker for diseases: Biomedical applications of AFM. AIP Conf. Proc. 1760, 020057 (2016).

    Article  Google Scholar 

  17. M.N. Starodubtseva: Mechanical properties of cells and ageing. Ageing Res. Rev. 10, 16 (2011).

    Article  Google Scholar 

  18. R.E. Mahaffy, S. Park, E. Gerde, J. Käs, and C.K. Shih: Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys. J. 86, 1777 (2004).

    Article  CAS  Google Scholar 

  19. K.E. Bremmell, A. Evans, and C.A. Prestidge: Deformation and nano-rheology of red blood cells: An AFM investigation. Colloids Surf., B 50, 43 (2006).

    Article  CAS  Google Scholar 

  20. M. Zhao and C. Srinivasan: Rate- and depth-dependent nanomechanical behavior of individual living Chinese hamster ovary cells probed by atomic force microscopy. J. Mater. Res. 21, 1906 (2006).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. E.M. Darling, S. Zauscher, and F. Guilak: Viscoelastic properties of zonal articular chondrocytes measured by atomic force microscopy. Osteoarthritis Cartilage 14, 571 (2006).

    Article  CAS  Google Scholar 

  23. E.J. Koay, A.C. Shieh, and K.A. Athanasiou: Creep indentation of single cells. J. Biomech. Eng. 125, 334 (2003).

    Article  Google Scholar 

  24. N.D. Leipzig and K.A. Athanasiou: Unconfined creep compression of chondrocytes. J. Biomech. 38, 77 (2005).

    Article  Google Scholar 

  25. A. Palmer, T.G. Mason, J. Xu, S.C. Kuo, and D. Wirtz: Diffusing wave spectroscopy microscopy of actin filament networks. Biophys. J. 76, 1063 (1999).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. A.H.W. Ngan and B. Tang: Response of power-law-viscoelastic and time-dependent materials to rate jumps. J. Mater. Res. 24, 853 (2009).

    Article  CAS  Google Scholar 

  28. B. Tang and A.H.W. Ngan: Nanoindentation using an atomic force microscope. Philos. Mag. 91, 1329 (2011).

    Article  CAS  Google Scholar 

  29. B. Tang and A.H.W. Ngan: Investigation of viscoelastic properties of amorphous selenium near glass transition using depth-sensing indentation. Soft Mater. 2, 125 (2004).

    Article  CAS  Google Scholar 

  30. E.K. Dimitriadis, F. Horkay, J. Maresca, B. Kachar, and R.S. Chadwick: Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys. J. 82, 2798 (2002).

    Article  CAS  Google Scholar 

  31. X.Y. Zhu, N. Zhang, Z.B. Wang, and X.P. Liu: Investigation of work of adhesion of biological cell (human hepatocellular carcinoma) by AFM nanoindentation. J. Micro-Bio Rob. 11, 47 (2016).

    Article  Google Scholar 

  32. T. Neumann: Determining the elastic modulus of biological samples using atomic force microscopy. JPK Instruments Application Report (2008).

    Google Scholar 

  33. Y. Liu, Z.B. Wang, and X.Y. Wang: AFM-based study of fullerenol (C60(OH)24)-induced changes of elasticity in living SMCC-7721 cells. J. Mech. Behav. Biomed. Mater. 45, 65 (2015).

    Article  CAS  Google Scholar 

  34. R.B. King: Elastic analysis of some punch problems for a layered medium. Int. J. Solids Struct. 23, 1657 (1987).

    Article  Google Scholar 

  35. J.M. Antunes, L.F. Menezes, and J.V. Fernandes: Three-dimensional numerical simulation of Vickers indentation tests. Int. J. Solids Struct. 43, 784 (2006).

    Article  CAS  Google Scholar 

  36. I.M. Ward and D.W. Hadley: An introduction to the mechanical properties of solid polymers, 2nd ed. (John Wiley & Sons Ltd, New York, 1993).

    Google Scholar 

  37. W.N. Findley, J.S. Lai, and K. Onaran: Creep and Relaxation of Nonlinear Viscoelastic Materials with an Introduction to Linear Viscoelasticity, 3rd ed. (Dover Publications, Inc, New York, 1989).

    Google Scholar 

  38. C.E. Hills, M.Y. Younis, J. Bennett, E. Siamantouras, K.K. Liu, and P.E. Squires: Calcium-sensing receptor activation increases cell–cell adhesion and β-cell function. Cell. Physiol. Biochem. 30, 575 (2012).

    Article  CAS  Google Scholar 

  39. J. Chen: Nanobiomechanics of living cells: A review. J. R. Soc., Interface 4, 20130055 (2014).

    Google Scholar 

  40. I.N. Sneddon: The relation between load and penetration in the axisymmetric Boussinesq problem for a punch of arbitrary profile. Int. J. Eng. Sci. 3, 47 (1965).

    Article  Google Scholar 

  41. E.H. Lee and J.R.M. Radok: The contact problem for viscoelastic bodies. J. Appl. Mech. 27, 438 (1960).

    Article  Google Scholar 

  42. T.C.T. Ting: The contact stresses between a rigid indenter and a viscoelastic half-space. J. Appl. Mech. 33, 845 (1966).

    Article  Google Scholar 

  43. H.L. Yu, Z. Li, and Q.J. Wang: Viscoelastic-adhesive contact modeling: Application to the characterization of the viscoelastic behavior of materials. Mech. Mater. 60, 55 (2013).

    Article  Google Scholar 

  44. J. Chen and G. Lu: Finite element modelling of nanoindentation based methods for mechanical properties of cells. J. Biomech. 45, 2810 (2012).

    Article  Google Scholar 

  45. J. Chen: Understanding the nanoindentation mechanisms of a microsphere for biomedical applications. J. Phys. D: Appl. Phys. 46, 495303 (2013).

    Article  CAS  Google Scholar 

  46. J. Sanchez-Adams, R.E. Wilusz, and F. Guilak: Atomic force microscopy reveals regional variations in the micromechanical properties of the pericellular and extracellular matrices of the meniscus. J. Orthop. Res. 31, 1218 (2013).

    Article  CAS  Google Scholar 

  47. N. Gavara and R.S. Chadwick: Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips. Nat. Nanotechnol. 7, 733 (2012).

    Article  CAS  Google Scholar 

  48. V. Vadillo-Rodriguez, T.J. Beveridge, and J.R. Dutcher: Surface viscoelasticity of individual Gram-negative bacterial cells measured using atomic force microscopy. J. Bacteriol. 190, 4225 (2008).

    Article  CAS  Google Scholar 

  49. Z.L. Zhou, A.H.W. Ngan, B. Tang, and A.X. Wang: Reliable measurement of elastic modulus of cells by nanoindentation in an atomic force microscope. J. Mech. Behav. Biomed. Mater. 8, 134 (2012).

    Article  CAS  Google Scholar 

  50. L. Sirghi, J. Ponti, F. Broggi, and F. Rossi: Probing elasticity and adhesion of live cells by atomic force microscopy indentation. Eur. Biophys. J. 37, 935 (2008).

    Article  CAS  Google Scholar 

  51. X.Y. Zhu, E. Siamantouras, K.K. Liu, and X.P. Liu: Determination of work of adhesion of biological cell under AFM bead indentation. J. Mech. Behav. Biomed. Mater. 56, 77 (2015).

    Article  Google Scholar 

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ACKNOWLEDGMENTS

The authors are grateful for the technical supports from the Laboratory of Precision Engineering and Surfaces of the University of Warwick and the International Research Centre for Nano Handling and Manufacturing, Changchun University of Science and Technology. This project has been partially funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 644971 and the China-EU research programme (S2016G4501).

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Zhu, X., Wang, Z. & Liu, X. Investigation of effect of fullerenol on viscoelasticity properties of human hepatocellular carcinoma by AFM-based creep tests. Journal of Materials Research 32, 2521–2531 (2017). https://doi.org/10.1557/jmr.2017.229

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