Programa del congreso

1. Introduction

Electroporation is a biophysical phenomenon in which exposure to electric fields increases cell membrane permeability to otherwise impermeable extracellular molecules by forming transient pores in the membrane. When reversible, this state enables therapeutic cellular transport; when irreversible, it leads to programmed cell death. and generated multiple medical treatments. The clinical applications of electroporation, which include electrochemotherapy (ECT), gene electrotransfer (GET), irreversible electroporation (IRE), and Calcium electroporation, show promising perspective for future therapies in oncology, cardiology, DNA vaccines, muscular disorders, and other fields [1]. However, the underlying physical mechanisms of electroporation are incompletely understood. In particular, it remains unclear why cell membrane permeability, as indicated by impedance measurements, continues to increase during electric field exposure and why elevated permeability persists long after the field has been removed. This study conducts a numerical investigation to determine whether Joule heating, which is expected to be intense within the pores formed during electroporation, can produce temperature increases sufficient to locally affect the structural integrity of the cell membrane, potentially serving as a contributing mechanism.

2. Methods

An electroporated cell membrane patch containing one or more pores was modelled on the finite element method simulation platform, COMSOL Multiphysics 6.0. The study first simulated the dynamic temperature increase resulting from the application of a 100 µs square electric pulse. Subsequently, static temperature distributions, corresponding to permanent field exposures, were analysed as a function of pore size, geometry, and density to explore their influence on temperature elevation.

3. Results and Discussion

The results indicate that the temperature increases are minimal (< 0.1 K) and negligible with respect to membrane disruption, suggesting that Joule heating within pores is very unlikely to contribute to the electroporation phenomenon. However, it must be noted that the effect of Joule heating on electroporation is scale dependent. While this study shows that Joule heating has a negligible impact on the nanoscale mechanism of pore formation itself, its macroscopic effects on tissue are significant. At the tissue level, Joule heating increases local electrical conductivity, thereby redistributing the electric field. This effect is particularly critical when non-uniform fields are applied, such as with needle electrodes [2], [3], [4].

References

[1] K. Rakoczy et al., ‘Electroporation in Clinical Applications—The Potential of Gene Electrotransfer and Electrochemotherapy’, Applied Sciences, vol. 12, no. 21, p. 10821, Oct. 2022, doi: 10.3390/app122110821.

[2] N. Beitel-White et al., ‘Multi-Tissue Analysis on the Impact of Electroporation on Electrical and Thermal Properties’, IEEE Transactions on Biomedical Engineering, vol. 68, no. 3, pp. 771–782, Mar. 2021, doi: 10.1109/TBME.2020.3013572.

[3] U. Pliquett, ‘Mechanistic studies of molecular transdermal transport due to skin electroporation’, Advanced Drug Delivery Reviews, vol. 35, no. 1, pp. 41–60, Jan. 1999, doi: 10.1016/S0169-409X(98)00062-3.

[4] A. H. Ruarus, L. G. P. H. Vroomen, R. S. Puijk, H. J. Scheffer, T. J. C. Faes, and M. R. Meijerink, ‘Conductivity Rise During Irreversible Electroporation: True Permeabilization or Heat?’, Cardiovasc Intervent Radiol, vol. 41, no. 8, pp. 1257–1266, Aug. 2018, doi: 10.1007/s00270-018-1971-7.