Modeling cell and tissue electroporation

Abstract

Large, pulsed electric fields are becoming an increasingly important tool in drug delivery, gene delivery, and apoptosis induction. Nonetheless, much remains unknown about the fundamental mechanisms by which large electric fields interact with cells and tissue, in part because many critical features of the cell and tissue responses occur on time and length scales that are difficult to assess experimentally. Therefore, sophisticated models are needed to further understanding of the basic mechanisms of interaction. Electroporation, in which transient, aqueous pores form in lipid bilayers, is one fundamental mechanism by which large electric fields may alter biological systems. Here cell and tissue electroporation models are presented that are based on the asymptotic model of electroporation and the new mesh transport network method (MTNM), which utilizes equivalent circuit networks to simulate nonlinear, coupled transport phenomena. The cell system simulations show that small magnitude (0.1 MV/m), long duration (100 [mu]s) pulses result in conventional electroporation, in which pores form in only the plasma membrane, while large magnitude (10 MV/m), short duration (10 ns) pulses result in supra-electroporation, in which pores form in the plasma membrane and organelle membranes.

(cont.) The organelle membrane electroporation may be a primary mechanism by which large magnitude, short duration pulses lead to complex, experimentally observed responses, including apoptosis. The tissue system simulations show that dynamic spatial shifts in the electric field accompany electroporation. For certain pulses, the shifting electric field can lead to quite spatially extensive tissue electroporation. The models presented here offer new insights into the dynamic electrical responses of cells and tissue to pulses of widely varying strength and duration and will contribute to the development of new therapies and biotechnologies based on electroporation.