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A Microdosimetric Study of Electropulsation on Multiple Realistically Shaped Cells: Effect of Neighbours

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Abstract

Over the past decades, the effects of ultrashort-pulsed electric fields have been used to investigate their action in many medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). Promising aspects of these pulses has led to several in vitro and in vivo experiments to clarify their action. Since the basic mechanisms of these pulses have not yet been fully clarified, scientific interest has focused on the development of numerical models at different levels of complexity: atomic (molecular dynamic simulations), microscopic (microdosimetry) and macroscopic (dosimetry). The aim of this work is to demonstrate that, in order to predict results at the cellular level, an accurate microdosimetry model is needed using a realistic cell shape, and with their position and packaging (cell density) characterised inside the medium.

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References

  • Bajorski P (2011) Statistics for imaging, optics, and photonics. Wiley, Sanford Weisberg

    Book  Google Scholar 

  • Benassi B, Filomeni G, Montagna C, Merla C, Lopresto V, Pinto R, Marino C, Consales C (2015) Extremely Low Frequency Magnetic Field (ELF-MF) exposure sensitizes SH-SY5Y cells to the pro-parkinson’s disease toxin MPP+. Mol Neurobiol. doi:10.1007/s12035-015-9354-4

    PubMed  Google Scholar 

  • Bettan M, Ivanov MA, Mir LM, Boissière F, Delaere P, Scherman D (2000) Effic DNA Electrotrans into Tumors Bioelectrochem 52:83–90

    CAS  Google Scholar 

  • Breton M, Mir LM (2012) Microsecond and nanosecond electric pulses in cancer treatments. Bioelectromagnetics 33:106–123

    Article  PubMed  Google Scholar 

  • Cadossi R, Ronchetti M, Cadossi M (2014) Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. Futur Oncol 10:877–890

    Article  CAS  Google Scholar 

  • Casciola M, Bonhenry D, Liberti M, Apollonio F, Tarek M (2014) A molecular dynamic study of cholesterol rich lipid membranes: comparison of electroporation protocols. Bioelectrochemistry 100:11–17

    Article  CAS  PubMed  Google Scholar 

  • Čorović S, Pavlin M, Miklavčič D (2007) Analytical and numerical quantification and comparison of the local electric field in the tissue for different electrode configurations. Biomed Eng Online 6:37–50

    Article  PubMed  PubMed Central  Google Scholar 

  • Denzi A, Merla C, Camilleri P, Paffi A, d’Inzeo G, Apollonio F, Liberti M (2013) Microdosimetric study for nanosecond pulsed electric fields on a cell circuit model with nucleus. J Membr Biol 246:761–767

    Article  CAS  PubMed  Google Scholar 

  • Denzi A, Strigari L, Di Filippo F, Botti C, Di Filippo S, Perracchio L, Ronchetti M, Cadossi R, Liberti M (2015a) Modeling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case. Biomed Eng Online 14(Suppl):3

    Google Scholar 

  • Denzi A, Merla C, Palego C, Paffi A, Ning Y, Multari CR, Cheng X, Apollonio F, Hwang JCM, Liberti M (2015b) Assessment of cytoplasm conductivity by nanosecond pulsed electric fields. IEEE Trans Biomed Eng 62:1595–1603

    Article  PubMed  Google Scholar 

  • Ermolina I, Polevaya Y, Feldman Y (2000) Analysis of dielectric spectra of eukaryotic cells by computer modeling. Eur Biophys J 29:141–145

    Article  CAS  PubMed  Google Scholar 

  • Esser AT, Smith KC, Gowrishankar TR, Weaver JC (2007) Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue. Technol Cancer Res Treat 6:261–273

    Article  PubMed  Google Scholar 

  • Esser AT, Smith KC, Gowrishankar TR, Weaver JC (2009) Towards solid tumor treatment by nanosecond pulsed electric fields. Technol Cancer Res Treat 8:289–306

    Article  PubMed  Google Scholar 

  • Gonzalez RC, Woods RE (2002) Digital image processing. Prentice Hall Upper Saddle River, New Jersey

    Google Scholar 

  • Gowrishankar TR, Weaver JC (2003) An approach to electrical modeling of single and multiple cells. Proc Natl Acad Sci USA 100:3203–3208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gowrishankar TR, Weaver JC (2006) Electrical behavior and pore accumulation in a multicellular model for conventional and supra-electroporation. Biochem Biophys Res Commun 349:643–653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gowrishankar TR, Smith KC, Weaver JC (2013) Transport-based biophysical system models of cells for quantitatively describing responses to electric fields. Proc IEEE 101:505–517

    Article  Google Scholar 

  • Guo F, Yao C, Li C, Mi Y (2013) Simulation study of trans-membrane potential of plasma and nuclear membranes with frequency dispersion. Trans China Electrotech Soc 28:182–188

    Google Scholar 

  • Ho MC, Casciola M, Levine ZA, Vernier PT (2013) Molecular dynamics simulations of ion conductance in field-stabilized nanoscale lipid electropores. J Phys Chem B 117:11633–11640

    Article  CAS  PubMed  Google Scholar 

  • Jain AK (1989) Fundamentals of digital image processing. Prentice-Hall, California

    Google Scholar 

  • Jiang C, Davalos RV, Bischof JC (2015) A review of basic to clinical studies of irreversible electroporation therapy. IEEE Trans Biomed Eng 62:4–20

    Article  PubMed  Google Scholar 

  • Joshi RP, Hu Q (2011) Case for applying subnanosecond high-intensity, electrical pulses to biological cells. IEEE Trans Biomed Eng 58:2860–2866

    Article  PubMed  Google Scholar 

  • Joshi RP, Schoenbach KH (2010) Bioelectric effects of intense ultrashort pulses. Critical Reviews™. Biomed Eng 38(3):55–304

    Google Scholar 

  • Joshi RP, Mishra A, Schoenbach KH (2008) Model assessment of cell membrane breakdown in clusters and tissues under high-intensity electric pulsing. IEEE Trans Plasm Sci 36:1680–1688

    Article  Google Scholar 

  • Kotnik T, Miklavčič D (2000) Theoretical evaluation of the distributed power dissipation in biological cells exposed to electric fields. Bioelectromagnetics 21:385–394

    Article  CAS  PubMed  Google Scholar 

  • Kotnik T, Pucihar G, Miklavčič D (2010) Induced transmembrane voltage and its correlation with electroporation-mediated molecular transport. J Membr Biol 236:3–13

    Article  CAS  PubMed  Google Scholar 

  • Merla C, Liberti M, Apollonio F, d’Inzeo G (2009) Quantitative assessment of dielectric parameters for membrane lipid bi-layer from RF permittivity measurements. Bioelectromagnetics 30:286–298

    Article  CAS  PubMed  Google Scholar 

  • Merla C, Paffi A, Apollonio F, Leveque P, d’Inzeo G, Liberti M (2011) Microdosimetry for nanosecond pulsed electric field applications: a parametric study for a single cell. IEEE Trans Biomed Eng 58:1294–1302

    Article  PubMed  Google Scholar 

  • Merla C, Denzi A, Paffi A, Casciola M, d’Inzeo G, Apollonio F, Liberti M (2012) Novel passive element circuits for microdosimetry of nanosecond pulsed electric fields. IEEE Trans Biomed Eng 59:2302–2311

    Article  CAS  PubMed  Google Scholar 

  • Mezeme ME, Pucihar G, Pavlin M, Brosseau C, Miklavčič D (2012) A numerical analysis of multicellular environment for modeling tissue electroporation. Appl Phys Lett 100:143701

    Article  Google Scholar 

  • Miklavcic D, Puc M (2006) Electroporation, Wiley Encyclopedia of Biomedical Engineering. John Wiley, Newyork

    Google Scholar 

  • Neal RE II, Davalos RV (2009) The feasibility of irreversible electroporation for the treatment of breast cancer and other heterogeneous systems. Ann Biomed Eng 37:2615–2625

    Article  PubMed  Google Scholar 

  • Neumann E, Rosenheck K (1972) Permeability changes induced by electric impulses in vesicular membranes. J Membr Biol 10:279–290

    Article  CAS  PubMed  Google Scholar 

  • Pavlin M, Pavšelj N, Miklavčič D (2002) Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system. IEEE Trans Biomed Eng 49:605–612

    Article  PubMed  Google Scholar 

  • Piuzzi E, Merla C, Cannazza G, Zambotti A, Apollonio F, Cataldo A, D’Attanasio P, De Benedetto E, Liberti M (2013) A comparative analysis between customized and commercial system for complex permittivity measurements on liquid samples at microwave frequencies. IEEE Trans Instrum Measurements 62:1034–1046

    Article  CAS  Google Scholar 

  • Polk C, Postov E (1995) Biological effects of electromagnetic fields. CRC handbook, 2nd edn. CRC, Boca Raton

    Google Scholar 

  • Pucihar G, Kotnik T, Valic B, Miklavcic D (2006) Numerical determination of transmembrane voltage induced on irregularly shaped cells. Annals Biomed Eng 34:642–652

    Article  CAS  Google Scholar 

  • Pucihar G, Kotnik T, Teissié J, Miklavčič D (2007) Electropermeabilization of dense cell suspensions. Eur Biophys J 36:173–185

    Article  PubMed  Google Scholar 

  • Pucihar G, Miklavcic D, Kotnik T (2009) A time-dependent numerical model of transmembrane voltage inducement and electroporation of irregularly shaped cells. IEEE Trans Biomed Eng 56:1491–1501

    Article  PubMed  Google Scholar 

  • Ramos A (2010) Improved numerical approach for electrical modeling of biological cell clusters. Med Biol Eng Comput 48:311–319

    Article  PubMed  Google Scholar 

  • Smith KC, Gowrishankar TR, Esser AT, Stewart D, Weaver JC (2006) The spatially distributed dynamic transmembrane voltage of cells and organelles due to 10 ns pulses: meshed transport networks. IEEE Trans Plasm Sci 34:1394–1404

    Article  Google Scholar 

  • Susil R, Šemrov D, Miklavcic D (1998) Electric Field-Induced Transmembrane Potential Depends on Cell Density and Organization. Electromagn Biol Med 17:391–399

    Google Scholar 

  • Teissié J, Escoffre JM, Paganin A, Chabot S, Bellard E, Wasungu L, Rols MP, Golzio M (2012) Drug delivery by electropulsation: recent developments in oncology. Int J Pharm 423:3–6

    Article  PubMed  Google Scholar 

  • Tieleman DP (2004) The molecular basis of electroporation. BMC Biochem 5:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Towhidi L, Kotnik T, Pucihar G, Firoozabadi SMP, Mozdarani H, Miklavcic D (2008) Variability of the minimal transmembrane voltage resulting in detectable membrane electroporation. Electromagn Biol Med 27:372–385

    Article  CAS  PubMed  Google Scholar 

  • Weaver JC, Smith KC, Esser AT, Son RS, Gowrishankar TR (2012) A brief overview of electroporation pulse strength–duration space: a region where additional intracellular effects are expected. Bioelectrochemistry 87:236–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This project was performed within the framework of the Joint IIT-Sapienza LAB on Life-NanoScience Project (81/13 16-04-2013) and by the COST Action TD1104—European network for the development of electroporation-based technologies and treatments (EP4Bio2Med). Thanks to Prof. MH Repacholi, University of Rome “La Sapienza” for his review and editorial support.

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Authors and Affiliations

  1. Center for Life Nano Science at Sapienza, Istituto Italiano di Tecnologia, Rome, Italy

    Agnese Denzi

  2. Department of Information Engineering, Electronics and Telecommunication (DIET), Italian Inter-University Centre of Electromagnetic Fields and Bio-Systems (ICEmB), University of Rome “La Sapienza”, 00184, Rome, Italy

    Agnese Denzi, Francesca Camera, Alessandra Paffi, Francesca Apollonio & Micaela Liberti

  3. Division of Health Protection Technologies, ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development, 00123, Rome, Italy

    Caterina Merla, Barbara Benassi & Claudia Consales

  4. Vectorology and Anticancer Therapies, UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, 94805, Villejuif, France

    Caterina Merla

Authors
  1. Agnese Denzi
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  2. Francesca Camera
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  3. Caterina Merla
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  4. Barbara Benassi
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  5. Claudia Consales
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  6. Alessandra Paffi
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  7. Francesca Apollonio
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  8. Micaela Liberti
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Corresponding author

Correspondence to Micaela Liberti.

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Denzi, A., Camera, F., Merla, C. et al. A Microdosimetric Study of Electropulsation on Multiple Realistically Shaped Cells: Effect of Neighbours. J Membrane Biol 249, 691–701 (2016). https://doi.org/10.1007/s00232-016-9912-3

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  • DOI: https://doi.org/10.1007/s00232-016-9912-3

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