Effect of pulsed electric fields on cell-cell-communication via gap junctions in cell-monolayers

Abstract

Summary form only given. Pulsed electric fields can charge the membranes of biological cells and as a result change cell morphologies and cell functions. Subcellular structures are stronger affected by exposures to pulses with durations that are short in comparison with the charging time of the cell's boundary. Conversely, longer pulses primarily affect the outer membrane. As a consequence there is a wide range of opportunities for applications, depending on pulse duration and pulse amplitude. The formation of pores in the plasma membrane, also known as electroporation, can be used to deliver drugs and genes into cells. Effects on organelles can change subcellular biochemistry and trigger cascade pathways such as the induction of apoptosis1. The latter mechanism is currently exploited as potentially novel cancer therapy. Studies so far have mostly focused on the interaction between pulsed electric fields and individual cells in vitro or on empirical investigations of treatment efficacies in vivo. However, an understanding of therapies that are based on pulsed electric fields further requires closing our gap in knowledge about processes affecting connected cells, i.e. the response of tissues. In fact communication between cells or impairment of communication pathways is a crucial factor in many diseases 2. The topic of our investigations are pulsed electric field effects on tissue with respect to tissue structures and properties and thus in particular the effect on the propagation of a stimulus across several cells. Cell-cell-communication via gap junctions will be examined by injecting a fluorescent dye into a single cell of a monolayer of liver cells. The propagation of the dye to adjacent cells after the exposure to a pulsed electric field will be compared to the propagation in unexposed cells. Concurrently special attention will be paid to the response at different temperatures. Based on our findings we hypothesize to be able to manipulate cell-cellcommunication with pulsed electric fields and possibly provide an additional pathway to increase treatment efficacies.