Dose-dependent 60Co γ-radiation Effects on Human Endothelial Cell Mechanical Properties

  • Alireza Mohammadkarim
  • Manijhe Mokhtari-DizajiEmail author
  • Ali Kazemian
  • Hazhir Saberi
  • Mohammad Mehdi Khani
  • Mohsen Bakhshandeh
Original Paper


Exposure to ionizing radiation is unavoidable for noncancerous cells during the external radiotherapy process. Increasing the dose delivery fraction times leads to increasing the endothelial cell damage. Vascular abnormalities are commonly associated with the alternation of endothelium biomechanical properties. The goal of the present study was to quantify the elastic and viscoelastic properties of human umbilical vein endothelial cells (HUVECs) using the micropipette aspiration technique in conjunction with a theoretical model while an 8 Gy dose was given in four fractions. Confocal imaging was performed for evaluation of cytoskeletal changes during fractionation 60Co radiotherapy. The results indicated an increase in elastic modulus from 29.87 ± 1.04 Pa to 46.69 ± 1.17 Pa while the fractional doses increased from 0 Gy to 8 Gy along with the obvious cytoskeletal changes. Moreover, in the creep behavior of radiated groups, a significant decrease was shown in the time constant and viscoelastic properties. On the other hand, it was observed that the change in the biomechanical properties of the cells while applying a single fraction of 8 Gy was not exactly the same as that in the properties of the radiation-exposed cells while delivering an 8 Gy dose at 2 Gy per fraction. The observed differences in the biomechanical behavior of endothelium provide a quantitative description of radiobiological effects for evaluating the dose-response relationship as a biological dosimetry procedure.


Fractionation radiotherapy Micropipette aspiration Confocal imaging Dose-response Endothelial cells 



This study was approved by Tarbiat Modares University. This work was supported in part by the Iran National Science Foundation (INSF).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Kern, P. M., Keilholz, L., Forster, C., Hallmann, R., Herrmann, M., & Seegenschmiedt, M. (2000). Low-dose radiotherapy selectively reduces adhesion of peripheral blood mononuclear cells to endothelium in vitro. Radiotherapy and Oncology, 54, 273–282.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Connor, P. (2013). The impact of missed fractions in head and neck radiotherapy and how they can be minimized. Radiography, 19, 343–346.CrossRefGoogle Scholar
  3. 3.
    Han, D., Hao, S., Tao, C., Zhao, Q., Wei, Y., Song, Z., & Li, B. (2015). Comparison of once daily radiotherapy to 60 Gy and twice daily radiotherapy to 45 Gy for limited stage small-cell lung cancer. Thoracic Cancer, 6, 643–648.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Ren, X., Wang, Q., Zhang, R., Chen, X., Wang, N., Liu, Y., Zong, J., Guo, Z., Wang, D., & Lin, Q. (2016). Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: Preliminary results of an early terminated phase II trial. BMC Cancer, 16, 1–13.CrossRefGoogle Scholar
  5. 5.
    Howlett, S., Duggan, L., Bazley, S., & Kron, T. (1999). Selective in vivo dosimetry in radiotherapy using p-type semiconductor diodes: A reliable quality assurance procedure. Medical Dosimetry, 24, 53–56.PubMedCrossRefGoogle Scholar
  6. 6.
    Travis, L. B., Ng, A. K., Allan, J. M., Pui, C., Kennedy, A. R., Xu, X. G., Purdy, J. A., Applegate, K., Yahalom, J., Constine, L. S., Gilbert, E. S., & Boice, Jr., J. D. (2012). Second malignant neoplasms and cardiovascular disease following radiotherapy. Journal of the National Cancer Institute, 104, 357–370.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Gujral, D. M., Shah, B. N., Chahal, N. S., Bhattacharyya, S., Senior, R., Harrington, K. J., & Nutting, C. M. (2016). Arterial stiffness as a biomarker of radiation-induced carotid atherosclerosis. Angiology, 67, 266–271.PubMedCrossRefGoogle Scholar
  8. 8.
    Gujral, D. M., Shah, B. N., Chahal, N. S., Senior, R., Harrington, K. J., & Nutting, C. M. (2014). Clinical features of radiation-induced carotid atherosclerosis. Clinical Oncology, 26, 94–102.PubMedCrossRefGoogle Scholar
  9. 9.
    Bischof, M., Abdollahi, A., Gong, P., Stoffregen, C., Lipson, K. E., Debus, J., Weber, K. J., & Huber, P. E. (2004). The triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR2 in human endothelial and tumor cells. International Journal of Radiation Oncology, Biology, Physics, 60, 1220–1232.PubMedCrossRefGoogle Scholar
  10. 10.
    Cheng, S. W. K., Ting, A. C. W., & Wu, L. L. H. (2002). Ultrasonic analysis of plaque characteristics and intimal-medial thickness in radiation-induced atherosclerotic carotid arteries. European Journal of Vascular and Endovascular Surgery, 24, 499–504.PubMedCrossRefGoogle Scholar
  11. 11.
    Martin, J. D., Buckley, A. R., Graeb, D., Walman, B., Salvain, A., Hsy, J. H., & Chir, M. B. B. (2005). Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation. International Journal of Radiation Oncology, Biology, Physics, 63, 1197–1205.PubMedCrossRefGoogle Scholar
  12. 12.
    Mcdonald, M. W., Moore, M. G., & Johnstone, P. A. S. (2012). Risk of carotid blowout after reirradiation of the head and neck: a systematic review. International Journal of Radiation Oncology, Biology, Physics, 82, 1083–1089.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang, B., Liu, B., Zhang, H., & Wang, J. (2014). Erythrocyte stiffness during morphological remodeling induced by carbon ion radiation. PLoS ONE, 9, 1–19.Google Scholar
  14. 14.
    Zheng, Q., Liu, Y., Zhou, H. J., Du, Y. T., Zhang, B. P., Zhang, J., Miao, G. Y., Liu, B., & Zhang, H. (2015). X-ray radiation promotes the metastatic potential of tongue squamous cell carcinoma cells via modulation of biomechanical and cytoskeletal properties. Human & Experimental Toxicology, 34, 894–903.CrossRefGoogle Scholar
  15. 15.
    Daar, E., Kaabar, W., Woods, E., Lei, C., Nisbet, A., & Bradley, D. A. (2014). Atomic force microscopy and mechanical testing of bovine pericardium irradiated to radiotherapy doses. Radiation Physics and Chemistry, 96, 176–180.CrossRefGoogle Scholar
  16. 16.
    Pachenari, M., Seyedpour, S. M., Janmaleki, M., Babazadeh, S., Taranejoo, S., & Hosseinkhani, H. (2014). Mechanical properties of cancer cytoskeleton depend on actin filaments to microtubules content: Investigating different grades of colon cancer cell lines. Journal of Biomechanics, 47, 373–379.PubMedCrossRefGoogle Scholar
  17. 17.
    Hatami, J., Tafazzoli-Shadpour, M., Haghipour, N., Shokrgozar, M. A., & Janmaleki, M. (2013). Influence of cyclic stretch on mechanical properties of endothelial cells. Experimental Mechanics, 53, 1291–1298.CrossRefGoogle Scholar
  18. 18.
    Sato, M., Theret, D. P., Wheeler, L. T., Ohshima, N., & Nerem, R. M. (1990). Application of micropipette technique to measurement of cultured porcine aortic endothelial cell viscoelastic properties. Journal of Biomechanical Engineering, 112, 263–268.PubMedCrossRefGoogle Scholar
  19. 19.
    Khani, M., Tafazzoli-Shadpour, M., Goli-Mlekabadi, Z., & Haghipour, N. (2015). Mechanical characterization of human mesenchymal stem cells subjected to cyclic uniaxial strain and TGF-β1. Journal of the Mechanical Behavior of Biomedical Materials, 43, 18–25.PubMedCrossRefGoogle Scholar
  20. 20.
    Gabrys, D., Greco, O., Patel, G., Prise, K. M., Tozer, G. M., & Kanthou, G. (2007). Radiation effects on the cytoskeleton of endothelial cells and endothelial monolayer permeability. International Journal of Radiation Oncology, Biology, Physics, 69, 1553–1562.PubMedCrossRefGoogle Scholar
  21. 21.
    Jelonek, K., Walaszczyk, A., Gabrys, D., Pietrowska, M., Kanthou, C. C., & Widlak, P. (2011). Cardiac endothelial cells isolated from mouse heart: A novel model for radiobiology. Acta Biochimica Polonica, 58, 397–404.PubMedGoogle Scholar
  22. 22.
    Kaffas, A. E., Al-Mahrouki, A., Tran, W. T., Giles, A., & Czarnota, G. J. (2014). Sunitinib effects on the radiation response of endothelial and breast tumor cells. Microvascular Research, 92, 1–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Sharma, P., Templin, T., & Grabham, P. (2013). Short-term effects of gamma radiation on endothelial barrier function: Uncoupling of PECAM-1. Microvascular Research, 86, 11–20.PubMedCrossRefGoogle Scholar
  24. 24.
    Theret, D. P., Levesque, M. J., Sato, M., Nerem, R. M., & Wheeler, L. T. (1988). The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements. Journal of Biomechanical Engineering, 110, 190–199.PubMedCrossRefGoogle Scholar
  25. 25.
    Sato, M., Ohshima, N., & Nerem, R. M. (1996). Viscoelastic properties of cultured porcine aortic endothelial cells exposed to shear stress. Journal of Biomechanics, 29, 461–467.PubMedCrossRefGoogle Scholar
  26. 26.
    Guilak, F., Tedrow, J. R., & Burgkart, R. (2000). Viscoelastic properties of the cell nucleus. Biochemical and Biophysical Research Communications, 269, 781–786.PubMedCrossRefGoogle Scholar
  27. 27.
    Wang, Z., Zhao, Z., Lu, J., Chen, Z., Mao, A., Teng, G., & Liu, F. (2015). A comparison of biological effects of 125I seeds continuous low-dose-rate radiation and 60Co high-dose-rate gamma radiation on non-small cell lung cancer cells. PLoS ONE, 10, 1–11.Google Scholar
  28. 28.
    Shibamato, Y., Miyakawa, A., Otsuka, S., & Iwata, H. (2016). Radiobiology of hypofractionated stereotactic radiotherapy: What are the optimal fractionation schedules? Journal of Radiation Research, 57, 76–82.CrossRefGoogle Scholar
  29. 29.
    Huang, B. T., Lu, J. Y., Lin, P. X., Chen, J. Z., Li, D. R., & Chen, C. Z. (2015). Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy. Scientific Reports, 5, 1–9.CrossRefGoogle Scholar
  30. 30.
    Kim, K. S., Kim, J. E., Choi, K. J., Bae, S., & Kim, D. H. (2014). Characterization of DNA damage-induced cellular senescence by ionizing radiation in endothelial cells. International Journal of Radiation Biology, 90, 71–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Masoumi, H., Mokhtari-Dizaji, M., Arbabi, A., & Bakhshandeh, M. (2014). Determine the dose distribution using ultrasound parameters in MAGIC-f polymer gels. Dose Response, 13, 1–7.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Alireza Mohammadkarim
    • 1
  • Manijhe Mokhtari-Dizaji
    • 1
    Email author
  • Ali Kazemian
    • 2
  • Hazhir Saberi
    • 3
  • Mohammad Mehdi Khani
    • 4
  • Mohsen Bakhshandeh
    • 5
  1. 1.Department of Medical Physics, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  2. 2.Radiation Oncology Research Center, Cancer InstituteTehran University of Medical SciencesTehranIran
  3. 3.Department of Radiology, Imam Khomeini HospitalTehran University of Medical SciencesTehranIran
  4. 4.Department of Tissue Engineering and Regenerative Medicine, School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  5. 5.Department of Radiology Technology, Faculty of Paramedical SciencesShahid Beheshti University of Medical Sciences and Health ServicesTehranIran

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