Effects of electroporation of mammalian cells on cytoskeleton and intercellular connections

Abstract

Electroporation of mammalian cells affects several cellular components, including cytoskeleton and intercellular connections. This chapter describes the effects of electroporation alone or in combination with cytotoxic drugs or plasmid DNA on the components of cytoskeleton. Responses of cells to electroporation depend on the type of cells. In Chinese hamster ovary cells, mainly microtubule filaments were depolymerized following electroporation with microsecond pulses, with a recovery during 60 min, while recently the effect on the actin filaments in the cell cortex was also demonstrated. Electroporation of endothelial cells caused, besides depolymerization of microtubules, also depolymerization of actin filaments, while vimentin intermediate filaments were not affected. In addition, the loss of contractility and vascular endothelial cadherin (VE-cadherin) from the adherens cell junction was also observed. All these changes lead to increased permeability of endothelial cell monolayer. In tumor cells, electroporation does not cause depolymerization of actin filaments, but their rearrangement into stress fibers, lamellipodia, and filopodia. Electroporation with nanosecond pulses also affects actin filaments. Their depolymerization and disassembly of gap junctions were observed following exposure of cells to nanosecond pulses, while tight junctions were not significantly affected. The role of cytoskeletal filaments was also studied following electrochemotherapy and plasmid DNA electrotransfer into the cells demonstrating that cytoskeletal proteins are quicker and more severely affected following electrochemotherapy compared to electroporation alone and that the actin filaments play an active role in gene electrotransfer. Collectively, electroporation greatly affects cytoskeleton and intercellular connections in different types of cells and plays an important role in the transport of plasmid DNA into the cells and in the vascular changes observed after treatment with electrochemotherapy. However, studies are needed to fully elucidate the involvement of cytoskeleton and intercellular connection in different types of electroporation application, which will possibly lead to improved or new treatment options based on electroporation technology.