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

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.

A wide-band bio-chip for real-time optical detection of bioelectromagnetic interactions with cells

“…Our device is also fully biocompatible allowing cell growth and viability for at least 12 hours after cell plating over the GCCPW visibility windows and gold electrodes. The real-time monitoring of the cells is possible using inverted microscopes thanks to the use of the transparent conductive ground (ITO) covering the aperture on the ground plane, enabling also the possibility of detailed microdosimetric assessments of individual cells in their actual exposure conditions 67 , 68 . Suitability tests of the device for cell electropermeabilization and imaging using the fluorescence Yo-Pro-1 dye were performed.…”

Confocal Microscopy Improves 3D Microdosimetry Applied to Nanoporation Experiments Targeting Endoplasmic Reticulum

“…In order to reconstruct the realistic geometry representative of the real biological target we followed a procedure similar to the one of Denzi et al (2016), Hanna et al (2017). We employed the cell images provided by a confocal fluorescence microscope (Leica TCS SPE, Germany, 63×, 1.30 NA oil), that allows to visualize the different cell compartments treated with a specific fluorescent dye.…”

“…A numerical model was realized based on the dielectric properties of the cell as reported in Table 1 (Denzi et al, 2016). A parallelepiped box was used to represent the extracellular medium surrounding the cells.…”

Design of Electroporation Process in Irregularly Shaped Multicellular Systems

“…Γ + , Γ − are the outer and inner boundaries of the cell membranes, respectively, and the normal vectorn is taken outgoing the membrane boundary. In the simulations, the pulsed electric field is generated by using two parallel-plate electrodes placed at the top and bottom of the cell system (see Figure 1) and the electric potential for each cell compartment has been calculated by numerically solving Equation (19). Finally, the TMV is calculated as the difference between the electric potential on the inner and outer boundaries of each cell membrane:…”

“…Although EP is commonly used in biotechnology and medical applications, the molecular and cellular mechanisms of pore formation and stabilization during the electropermeabilization of membranes are still not fully understood and there are often discrepancies between experimental data and theoretical descriptions of pores creation [18]. Furthermore, the EP effectiveness depends on the cell type, specific structure of the biological membrane, the arrangement of the multicellular system as well as it is associated to the parameters defining the applied electric pulses such as the number, duration, frequency and intensity of the electric field [19,20]. Taking into account the EP effectiveness constraints and considering that the experimental measurements of the transmembrane voltage (TMV) is essentially limited by the thinness of the cell membrane as well as by the range of pulse duration, a numerical approach is often chosen to give a realistic description of the electric phenomena involved during EP process.…”