Effects of cell orientation and electric field frequency on the transmembrane potential induced in ellipsoidal cells

The transmembrane potential (Δϕ) induced by external electric fields is important both in biotech applications and in new medical therapies. We analyzed the effects of AC field frequency and cell orientation for cells of a general ellipsoidal shape. Simplified equations were derived for the membrane surface points where the maximum Δϕ is induced. The theoretical results were confirmed in experiments with three-axial chicken red blood cells (a:b:c = 6.66 μm:4.17 μm:1.43 µm). Propidium iodide (PI) staining and cell lysis were detected after an AC electropermeabilization (EP) pulse. The critical field strength for both effects increased when the shorter axis of a cell was parallel to the field, as well as at higher field frequency and for shorter pulse durations. Nevertheless, data analysis based on our theoretical description revealed that the Δϕ required is lower for the shorter axis, i.e. for smaller membrane curvatures. The critical Δϕ was independent of the field frequency for a given axis, i.e. the field strength had to be increased with frequency to compensate for the membrane dispersion effect. Comparison of the critical field strengths of PI staining in a linear field aligned along semi-axis a (142 kV m− 1) and a field rotating in the a–b plane (115 kV m− 1) revealed the higher EP efficiency of rotating fields.