title: Simulation Studies of Cellular Electroporation Due to Ultra-Fast Electric Pulses
Creators: name: Barthaki, Gayathri R.
Publisher: name: Old Dominion University
publisherIdentifier: https://ror.org/04zjtrb98
publisherIdentifierScheme: ROR
Year: 2000

description: Biological systems, from cells to ecosystems, are intrinsically complex information-processing networks. It often becomes difficult to predict their behavior during an experimental investigation, as their behavior is fundamentally chaotic, Hence, building models that mimic the dynamics of such systems and performing computer simulations would help in understanding, predicting, controlling and optimizing these systems. This thesis is aimed at the development of a mathematical model for the process of electroporation in biological cells when they are subjected to ultra-fast electric pulses and at conducting simulations to understand its dynamic behavior with special emphasis on the physics of ultra-short time scales.

With the recent progress in nanosecond pulsed-power technology and its application to biological systems, the sub-microsecond temporal regime has begun to assume great importance. It has been observed that when biological cells are subjected to high field electric pulses generated by pulsed-power sources, a number of changes like cellular response characteristics, structural shape and stability can be engineered. The electric pulses can produce irreversible changes, such as the eventual disintegration of cellular membranes, if they are of sufficiently high intensity and/or have long time duration. This can lead to the destruction of the organism as a whole, an effect that could find potential applications in the area of biological decontamination for improving hygiene, for sterilization or in neutralizing germ-attacks during warfare. Alternatively, the reversible electric field effects, wherein the cellular membrane expands and reseals upon the termination of electric field, could be used for the delivery of transdermal drugs and in gene therapy.

This thesis develops a mathematical model of pores on cellular membranes that are created upon the application of ultra-fast electric fields, and their dynamic evolution in response to such external electric fields. Numerical simulations were conducted to study the growth and resealing dynamics of the transient pores. The goals of the simulation study were (i) to gauge the voltage dependence of the cell membrane stability and (ii) to probe the role of the pulse width on pore dynamics. These simulations have shown that if the widths of the applied electric pulses were too short, cells would survive in spite of the application of large voltages. Irreversible breakdown conditions would then be avoided. Next, consideration of the pulse width dependence for irreversible breakdown showed that in the absence of dissipation, the input energy reduced to a limiting value with decreasing pulse widths. However, with the circuit effects taken into account, a local minimum in the pulse-dependent energy function was predicted. This was found to be in agreement with previously published experimental reports. Finally, this study puts forth an improved energy model, based on a time-dependent surface tension parameter, that explains the stability of the pores long after the termination of the electric pulses unlike the previous model.