Bioelectrorheological model of the cell. 4. Analysis of the extensil deformation of cellular membrane in alternating electric field

The bioelectrorheological model demonstrates the relationship between AEFs, shape deformations, and membrane destabilization, which can contribute to electroporation and other electric field-induced cell phenomena including electrofusion and electro-destruction.

“The bioelectrorheological model of the cell was proposed and has been expanded upon through a series of manuscripts by Pawlowski et al. [40,53,54,55,56,57] (Figure 3B). This model demonstrates the relationship between AEFs, shape deformations, and membrane destabilization, which can contribute to electroporation and other electric field-induced cell phenomena including electrofusion and electro-d”

The range of frequencies that results in high constant extensile stress values can be extended to include even higher frequencies by increasing the external medium conductivity.

“However, this range of frequencies that results in high constant extensile stress values can be extended to include even higher frequencies, by increasing the external medium conductivity (Table 1).”

The bioelectrorheological model provides a possible explanation for the causes of electroporation by demonstrating the combined effects of heat energy and extensile stress leading to reversible cell membrane destabilization, which can directly result in electroporation.

“Although the electric field strengths studied by Pawlowski and colleagues [40,53,54,55,56,57] were two orders of magnitude greater than that of TTFields, the bioelectrorheological model provides a possible explanation to the causes of electroporation by demonstrating the combined effects of heat energy and extensile stress leading to reversible cell membrane destabilization, which can directly”

In N. crassa, the maximum value of extensile stress was modeled as a function of electric field frequency (0.1 to 100,000 kHz) using an electric field strength of 250 V/cm, which is two orders of magnitude greater than the field strength of TTFields (1-4 V/cm).

“In N. crassa, the maximum value of extensile stress was modeled as a function of electric field frequency (ranging from 0.1 to 100,000 kHz) using an electric field strength (E) of 250 V/cm [40], which is two orders of magnitude greater than the field strength of TTFields (i.e., 1–4 V/cm).”

Extensile stress is influenced by membrane area and thickness as well as position on the membrane, and reaches maximum values at the poles and high values at the equator of the cell.

“It is influenced by membrane area and thickness as well as position on the membrane [40]. Stress which is calculated using Maxwell-Wagner polarization, Maxwell stress, mechanical normal, and tangential stress reaches maximum values at the poles and high values at the equator of the cell [40].”

Maximum extensile stress remains constantly high at low AEF frequencies and decreases in a sigmoidal fashion at higher frequencies.

“A graph of these results revealed that the maximum extensile stress remains constantly high at low AEF frequencies, and decreases in a sigmoidal fashion at higher frequencies [40].”

Extensile stress is dependent on the AEF's amplitude and frequency and the electric and geometric parameters of the cell system, including membrane dielectric properties and cell radius.

“Furthermore, extensile stress is dependent on the AEF’s amplitude and frequency and the electric and geometric parameters of the cell system, including membrane dielectric properties and cell radius [40].”

The bioelectrorheological model can be applied to extensile mechanical stress, observed with AEFs of 0.1 to 10,000 kHz, leading to destabilization of the cell membrane and eventually electroporation.

“The bioelectrorheological model of the cell can also be applied to extensile mechanical stress, which is observed with application of AEFs with frequencies of 0.1 to 10,000 kHz, and leads to destabilization of the cell membrane and, eventually, electroporation.”

Both DC and AC electroporation are believed to cause a dielectric breakdown of the cell; the oscillating nature of AC electroporation is thought to provoke structural fatigue of the membrane, comparable to the extensile stress proposed in the bioelectrorheological model.

“Both types of electroporation are believed to cause a dielectric breakdown of the cell. However, the oscillating nature of AC electroporation is thought to provoke structural fatigue of the membrane [61], comparable to the extensile stress proposed in the bioelectrorheological model [40,53,54,55,56,57].”

Membrane distortions predicted by the bioelectrorheological model are likely another feature of TTFields' actions.

“For example, TTFields have been reported to activate Cav2+ channels [46], membrane distortions predicted by the bioelectrorheological model are likely another feature of TTFields’ actions [40], and membrane fenestration is a hallmark of reversible electroporation [62].”