Electroporation of cells and tissues

Abstract

Electrical pulses that cause the transmembrane voltage of fluid lipid bilayer membranes to reach at least U/sub m//spl ap/0.2 V, usually 0.5-1 V, are hypothesized to create primary membrane "pores" with a minimum radius of -1 nm. Transport of small ions such as Na/sup +/ and Cl/sup -/ through a dynamic pore population discharges the membrane even while an external pulse tends to increase U/sub m/, leading to dramatic electrical behavior. Molecular transport through primary pores and pores enlarged by secondary processes provides the basis for transporting molecules into and out of biological cells. Cell electroporation in vitro is used mainly for transfection by DNA introduction, but many other interventions are possible, including microbial killing. Ex vivo electroporation provides manipulation of cells that are reintroduced into the body to provide therapy. In vivo electroporation of tissues enhances molecular transport through tissues and into their constitutive cells. Tissue electroporation, by longer, large pulses, is involved in electrocution injury. Tissue electroporation by shorter, smaller pulses is under investigation for biomedical engineering applications of medical therapy aimed at cancer treatment, gene therapy, and transdermal drug delivery. The latter involves a complex barrier containing both high electrical resistance, multilamellar lipid bilayer membranes and a tough, electrically invisible protein matrix.