Although electroporation is a well know technique with applications spanning from drug delivery to cancer therapy, the mechanisms involved in the phenomenon are still not well understood [1, 2]. In a recent study, we found that human lymphoblastoid Jurkat cells under a single, 60 ns, 2.5 MV/m pulsed electric field, exhibited differential uptake of the dyes YO-PRO1 and PI, right after pulse and over time, due to their molecular configuration [3]. The present study aims to compare the results of a 3D Finite Element Method numerical solution of the phenomenon with experimental findings, in order to validate the model and to increase the information about the involved mechanism. The proposed approach is based on a literature available model assuming that the pore dynamics is governed by an asymptotic form of the Smoluchosky equation [4], while the ionic flux through the electrically induced pores can be modelled by means of a suitable current source. The non linear dynamics of the electric responses of the membrane can be obtained by considering a cell model immersed in an electric field obtained by the Electro Quasi Static formulation of the Maxwell equations coupled with the ordinary differential equation describing the electroporation of the plasma membrane by means of a specific pore density population, N(r,VM(t),P) (r = pore radius, t = time, VM= voltage across the membrane and P = particular point on the membrane) [5]. The non linear equations system is then solved numerically in the time domain by means of a commercial software based on the Finite Element Method. The variables VM and N are used in order to check the activation of electroporation. The phenomenon is assumed to be activated when, upon the application of a nanosecond pulsed electric field (nsPEF), VM reaches a critical value and the pore density significantly overrides its equilibrium status. In order to associate numerical to experimental results, in a preliminary approach the model is implemented by assuming a fixed pore radius, whereas the hypothesis of the confluence of different pores in a greater, more stable pore will be subsequently explored.
INVESTIGATING THE ROLE OF PULSE REPETITION RATE IN MODULATING CELLULAR RESPONSE TO HIGH VOLTAGE, NANOSECOND ELECTRIC PULSES
Stefania Romeo;Anna Sannino;Olga Zeni
2012
Abstract
Although electroporation is a well know technique with applications spanning from drug delivery to cancer therapy, the mechanisms involved in the phenomenon are still not well understood [1, 2]. In a recent study, we found that human lymphoblastoid Jurkat cells under a single, 60 ns, 2.5 MV/m pulsed electric field, exhibited differential uptake of the dyes YO-PRO1 and PI, right after pulse and over time, due to their molecular configuration [3]. The present study aims to compare the results of a 3D Finite Element Method numerical solution of the phenomenon with experimental findings, in order to validate the model and to increase the information about the involved mechanism. The proposed approach is based on a literature available model assuming that the pore dynamics is governed by an asymptotic form of the Smoluchosky equation [4], while the ionic flux through the electrically induced pores can be modelled by means of a suitable current source. The non linear dynamics of the electric responses of the membrane can be obtained by considering a cell model immersed in an electric field obtained by the Electro Quasi Static formulation of the Maxwell equations coupled with the ordinary differential equation describing the electroporation of the plasma membrane by means of a specific pore density population, N(r,VM(t),P) (r = pore radius, t = time, VM= voltage across the membrane and P = particular point on the membrane) [5]. The non linear equations system is then solved numerically in the time domain by means of a commercial software based on the Finite Element Method. The variables VM and N are used in order to check the activation of electroporation. The phenomenon is assumed to be activated when, upon the application of a nanosecond pulsed electric field (nsPEF), VM reaches a critical value and the pore density significantly overrides its equilibrium status. In order to associate numerical to experimental results, in a preliminary approach the model is implemented by assuming a fixed pore radius, whereas the hypothesis of the confluence of different pores in a greater, more stable pore will be subsequently explored.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
