Electropermeabilization of mammalian cells. Quantitative analysis of the phenomenon.

Transient membrane permeabilization by application of high electric field intensity pulses on cells (electropermeabilization) depends on several physical parameters associated with the technique (pulse intensity, number, and duration). In the present study, electropermeabilization is studied in terms of flow of diffusing molecules between cells and external medium. Direct quantification of the phenomenon shows that electric field intensity is a critical parameter in the induction of permeabilization. Electric field intensity must be higher than a critical threshold to make the membrane permeable. This critical threshold depends on the cell size. Extent of permeabilization (i.e., the flow rate across the membrane) is then controlled by both pulse number and duration. Increasing electric field intensity above the critical threshold needed for permeabilization results in an increase membrane area able to be permeabilized but not due to an increase in the specific permeability of the field alterated area. The electroinduced permeabilization is transient and disappears progressively after the application of the electric field pulses. Its life time is under the control of the electric field parameters. The rate constant of the annealing phase is shown to be dependent on both pulse duration and number, but is independent of electric field intensity which creates the permeabilization. The phenomenon is described in terms of membrane organization transition between the natural impermeable state and the electro-induced permeable state, phenomenon only locally induced for electric field intensities above a critical threshold and expanding in relation to both pulse number and duration.