Industry 4.0
Vol. 8 (2023), Issue 1, pg(s) 12-18

DOMINANT TECHNOLOGIES IN “INDUSTRY 4.0”

Application of the mathematical model of Johnson-Kendall-Roberts in the study of the Young’s modulus of erythrocytes in patients with type 2 diabetes mellitus

  • 1 Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria; Centre of competence at Mechatronics and Clean Technologies – MIRACle, Sofia, Bulgaria
  • 2 Institute of Polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria
  • 3 Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria
  • 4 Clinic of Nervous Diseases, Uni Hospital, Panagyurishte, Bulgaria
  • 5 Bulgarian Society of Biorheology, Sofia, Bulgaria

Abstract

The goal of the present study is to evaluate the elastic properties (Young’s modulus) of erythrocytes from healthy donors and patients with type 2 diabetes mellitus (T2DM), by using an atomic force microscope (AFM). Morphological and mechanical characteristics of red blood cells are studied in parallel by PeakForce QNM (Quantitative NanoMechanical Mapping) mode of AFM Dimensional ICON Bruker NanoScope V9 Instrument. Young’s modulus is calculated based on the mathematical model of Johnson-Kendall-Roberts by the application of the “two-point method”. AFM images of the erythrocytes from the healthy donors show that erythrocytes with a normal biconcave shape predominate. In patients with T2DM, the so-called erythrocyte polymorphism is studied. The Young’s modulus of erythrocytes, in patients with T2DM, significantly statistically increases by 27% (p≤0,001), compared to the data of healthy donors. The studied Young’s modulus by AFM can be used in clinical practice as a precise biomarker for the state of the red blood cells in T2DM.

Keywords

References

  1. Guz, N., Dokukin, M., Kalaparth, V., Sokolov, I. If cell mechanics can be described by elastic modulus: study of different models and probes used in indentation experiments. Biophysical J., 107, 564-575 (2014).
  2. Sokolov, I., Dokukin, M. E., Guz, N. V. Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments. Methods 1, 60(2), 202-213 (2013).
  3. Yeow, N., Tabor, R. F., Garnier, G. Atomic force microscopy: From red blood cells to immunohaematology. Adv Colloid Interface Sci. 249, 149-162 (2017).
  4. Kim, J., Lee, H. Y., Shin S. Advances in the measurement of red blood cell deformability: A brief review. Journal of Cellular Biotechnology, 1, 63-79 (2015).
  5. Andreeva, T., Komsa-Penkova, R., Langari, A., et al. Morphometric and nanomechanical features of platelets from women with early pregnancy loss provide new evidence of the impact of inherited thrombophilia. Int J Mol Sci. 22(15):7778 (2021).
  6. Girasole, M., Pompeo, G., Cricenti, A., et al. Roughness of the plasma membrane as an independent morphological parameter to study RBCs: a quantitative atomic force microscopy investigation. Biochimica et Biophysica Acta, 1768(5), 1268-1276 (2007).
  7. Pretorius, E., Bester, J., Vermeulen, N., et al. Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics. Cardiovasc Diabetol. 14:30 (2015).
  8. Brun, J. F., Varlet-Marie, E., Myzia, J., de Mauverger, E. R., Pretorius, E. Metabolic influences modulating erythrocyte deformability and eryptosis. Metabolites, 12, 4 (2022).
  9. Rask-Madsen, C., King, L. G. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab. 17(1), 20-33 (2013).
  10. Cappella, B. Physical Principles of Force–Distance Curves by Atomic Force Microscopy. In: Cappella, B., Mechanical Properties of Polymers Measured through AFM Force-Distance Curves, Springer International Publishing Switzerland, 3-63 (2016).
  11. Garcia, R. Nanomechanical mapping of soft materialswith the atomic force microscope: methods, theory and applications. Chem. Soc. Rev. 49, 5850-5884 (2020).
  12. Dulinska, I., Dokukin, M. E., Guz, N. V. Method for quantitative measurements of the elastic modulus of biological cells in AFM indentation experiments. Methods 60, 202-213 (2013).
  13. Roa, J. J., Oncins, G., Diaz, J., Sanz, F., Segarra, M. Calculation of Young's modulus value by means of AFM. Recent Pat Nanotechnol, 5(1), 27-36 (2011).
  14. Zeng, G., Dirscherl, K., Garnæs, J. Accurate quantitative elasticity mapping of rigid nanomaterials by atomic force microscopy: effect of acquisition frequency, loading force, and tip geometry. Nanomaterials, 8, 616-628 (2018).
  15. Dokukin, M. E., Sokolov, I. Quantitative mapping of the elastic modulus of soft materials with HarmoniX and PeakForce QNM AFM modes. Langmuir 20;28(46):16060-71 (2012).
  16. Ladjal, H., Hanus, J.-L., Pillarisetti, A., et al. Atomic force microscopy-based single-cell indentation: Experimentation and finite element simulation. IEEE/RSJ International Conference on Intelligent Robots and Systems, Oct 2009, St. Louis, MO, United States, 1326-1332 (2009).
  17. Kuznetsova, T. G., Starodubtseva, M. N., Tegorenkov, et al. Atomic force microscopy probing of cell elasticity. Micron 38, 824- 833 (2007).
  18. Barthel, E. Adhesive elastic contacts: JKR and more. J. Phys. D: Appl. Phys. 41 163001 (2008).
  19. Grierson, D. S., Flater, E. E., Carpick, R. W. Accounting for the JKR–DMT transition in adhesion and friction measurements with atomic force microscopy. J. Adhesion Sci. Technol., 19(3–5), 291-311 (2005).
  20. Sun, Y., Akhremitchev, B., Walker G. C. Using the adhesive interaction between atomic force microscopy tips and polymer surfaces to measure the elastic modulus of compliant samples. Langmuir 20, 5837-5845 (2004).
  21. Chu, Y. S., Dufour, S., Thiery, J. P., Perez, E., Pincet, F. Johnson-Kendall-Roberts theory applied to living cells. Phys Rev Lett. 94(2):028102 (2005).
  22. Nakajima, K., Ito, M., Wang, D., Liu, H., et al. Nano-palpation AFM and its quantitative mechanical property mapping. Microscopy, 193-207 (2014).
  23. Meneghini L. Medical Management of Type 2 Diabetes. 8th ed. American Diabetes Association (2020).
  24. Alexandrova-Watanabe, A. Study of rheological, mechanical and morphological properties of blood, its formal elements and parameters of hemocoagulation in type 2 diabetes mellitus. PhD thesis, Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria (2021).
  25. Zeng, G., Dirscherl, K., Garnæs, J. Toward accurate quantitative elasticity mapping of rigid nanomaterials by atomic force microscopy: effect of acquisition frequency, loading force, and tip geometry. Nanomaterials, 8, 616-628 (2018).
  26. Dufrêne, Y. F., Martínez-Martín, D., Medalsy, I., et al. Multiparametric imaging of biological systems by force-distance curve-based AFM. Nat Methods, 10: 847–854 (2013).
  27. Pittenger, B., Erina, N., Su, C. Quantitative Mechanical Properties Mapping at the Nanoscale with PeakForce QNM. Bruker Application Note 128 (2011).
  28. Bruker. Dimension Icon User Guide. Bruker Corporation (2010).
  29. Fornal, M., Lekka, M., Pyka-Fościak, G., et al. Erythrocyte stiffness in diabetes mellitus studied with atomic force microscope. Clin Hemorheol Microcirc. 35(1-2), 273-276 (2006).
  30. Drozd, E. S., Chizhik, S. A., Konstantinova, E. E. Mechanical characteristics of erythrocyte membranes in patients with type 2 diabetes mellitus. Series on Biomechanics 25, 3-4, 53-60 (2010).
  31. Krastev, R. Study of the morphological and mechanical characteristics of the erythrocyte membrane. Dependence on the rheological properties of blood. Master's thesis, Faculty of Physics, Sofia University "St. Kliment Ohridski", Sofia, Bulgaria (2011).
  32. Antonova, N., Alexandrova, A., Melnikova, et al. Micromechanical properties of peripheral blood cells (erythrocytes, lymphocytes and neutrophils) in patients with diabetes mellitus type 2, examined with atomic force microscope (AFM). Series on Biomechanics 33 (4), 3-11 (2019).
  33. Efremov, Y. M., Wang, W.-H., Hardy, S. D., Geahlen R. L., Raman, A. Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves. Scientific Reports 7: 1541 (2017).
  34. Ciasca, G., Papi, M., Claudio, D. S., Chiarpotto, M., et al. Mapping viscoelastic properties of healthy and pathological red blood cells at the nanoscale level. Nanoscale 7, 17030-17037 (2015).
  35. Keymel, S., Heiss, C., Kleinbongard, P., et al. Impaired red blood cell deformability in patients with coronary artery disease and diabetes mellitus. Horm. Metab. Res. 43, 760-765 (2011).
  36. Lee, H., Na, W., Lee, S. B., Ahn, C. W., et al. Potential diagnostic hemorheological indexes for chronic kidney disease in patients with type 2 diabetes. Frontiers in Physiology 10:1062 (2019).
  37. AlSalhi, M. S., Devanesan, S., AlZahrani, K. E., et al. Impact of diabetes mellitus on human erythrocytes: atomic force microscopy and spectral investigations. Int J Environ Res Public Health 15:2368 (2018).
  38. Gyawali, P., Richards, R. S., Nwose, E. U. Erythrocyte morphology in metabolic syndrome. Expert Rev. Hematol. 5(5), 523-531 (2012).
  39. Shin, S., Ku, Y., Babu, N., Singh, M. Erythrocyte deformability and its variation in diabetes mellitus. Indian J Exp Biol. 45(1), 121-128 (2007).
  40. Rajab, A. M., Rahman, S., Rajab, T. M., Haider, K. H. Morphology and chromic status of red blood cells are significantly influenced by gestational diabetes. Diab Met Syndr: Clin Res Rev 7, 4, 140-148 (2018).

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