In Silico Assessment of Nanosecond Pulse Exposures of Cells, Tissues and Organs

摘要

Recent findings on the effect of submicrosecond, megavolt-per-meter electrical pulses (10-300 ns, 360-10 kV/cm) on cells have generated much interest in their use as a tool for manipulating intracellular processes. The underlying mechanism is hypothesized to be supra-electroporation, i.e., spatially uniform creation of a large number of small (<1 nm) transient openings in the plasma membrane and organelle membranes [1]. These studies are relatively new and, therefore, a great deal is unknown about the dynamics of supra-electroporation and the electrical and physiological effects of such extraordinary number of aqueous pores in the membrane. We have developed an in silico framework that integrates macro- and microdosimetry models, and incorporates biophysical mechanism models to estimate biochemical change resulting from exposure to nanosecond electrical pulses. This approach provides estimates of conductance changes and biochemical release/uptake within cells, local tissue regions and organs.