Time dependence of electric field effects on cell membranes. A review for a critical selection of pulse duration for therapeutical applications

Background. Electropulsation is one of the non-viral methods successfully used to transfer drugs and genes into living cells in vitro as in vivo. This approach shows promise in field of gene and cellular therapies. This presentation first describes the temporal factors controlling electropermeabilization to small molecules (< 4kDa) and then the processes supporting DNA transfer in vitro. The description of in vitro events brings our attention on the processes occurring before (s), during (ms) and after electropulsation (ms to hours) of DNA and cells. They all appear to be multistep events with well defined kinetics. They cannot be described as just punching holes in a lipid matrix in a two states process. Conclusions. The faster events (may be starting on the ns time scale) appear to be under the control of the external field while the slower ones are linked to the cell metabolism. Investigating the associated collective molecular reorganization by fast kinetics methods and molecular dynamics simulation will help in their safe developments for the in vivo processes and their present and potential clinical applications.