Frequency response model and simulation of transmembrane potentials on cellular inner and outer membranes

In order to calculate transmembrane potentials of both inner and outer membranes more accurately, this paper presented a multi-shelled dielectric model for spherical cell according to the structure of cell, because the influence of organelles such as nuclear on the electric field distribution should be account for. Based on this model, the general method for analyzing the frequency response of the transmembrane potential on cellular inner and outer membrane is proposed. From the simulation and analysis of the frequency response, it can be drawn that the frequency response of the transmembrane potential on cellular outer membrane shows first-order low-pass filter characteristic, while that on inner membrane can be treated as a first-order band-pass filter. The transmembrane potential on inner membrane not only keeps a higher value, but also exceeds that on outer membrane in the range from center to upper cut-off frequency of the frequency response of the transmembrane potential on inner membrane. This property is in favor to apply nanosecond pulsed electric field (nsPEF) to induce intracellular electromanipulation (IEM). After cells labeled with Rhodamine 123 were exposed to nanosecond pulses with durations of 130ns, 250ns and 600ns, respectively, the fluorescence intensity indicating the transmembrane potential on mitochondrial membrane was measured under laser scanning confocal microscope (LSCM). The experimental result agrees well with the simulation. Therefore, the simulation result provides a theoretical guidance to choosing reasonable window parameters for application of nanosecond pulse to tumor treatment.