Electrical conductance of lipid pores

Abstract

Electroporation (EP), also known as electropermeabilization, is a widely used technology employed primarily for intracellular delivery of drugs and genes, likewise for tissue and tumor destruction. The majority of the studies on EP hypothesize that the boost in permeability of cell membranes, following the application of pulsed electric fields, to low- and non-permeant molecules results from the formation of long lasting lipid defects, termed pores. However, the exact nature (morphology, size, number, etc.) of these pores is still unknown. Determining the pore size and their quantity under certain condition is crucial to understand, and eventually improve, the permeabilization efficiency. The main limit to the direct experimental observation of "lipid pores" is their nanometer range size, not appreciable by today's conventional techniques. Away to indirectly relate experimental observations to the size and numbers of pores, relying on simplified analytical formulas, is measuring the change in electrical conductance after the electropulsation. The investigation of EP with atomic detail has been possible, thanks to molecular dynamics (MD) simulations. In the past 10 years, extensive MD studies have been carried out to model the effect of PEFs on lipid bilayers, site of pore formation in cell membranes. Thanks to this method, the evaluation of structural (size) and electrical (conductance) properties of pores formed under conditions comparable to experiments is possible, providing information hardly accessible by direct observations. This chapter provides an overview of MD studies on the electrical conductance of lipid pores and how they relate to experiments.