Theoretical predictions of electromechanical deformation of cells subjected to high voltages for membrane electroporation

Abstract

An electromechanical analysis based on thin-shell theory is presented to analyze cell shape changes in response to external electric fields. This approach can be extended to include osmotic-pressure changes. Our calculations demonstrate that at large fields, the spherical cell geometry can be significantly modified, and even ellipsoidal forms would be inappropriate to account for the deformation. Values of the surface forces obtained from our calculations are in very good agreement with the 1--10 mN/m range for membrane rupture reported in the literature. The results, in keeping with reports in the literature, demonstrate that the final shape depends on membrane thickness. This has direct implications for tissues in which significant molecular restructuring can occur. It is also shown that, at least for the smaller electric fields, both the cellular surface area and volume change roughly in a quadratic manner with the electric field. Finally, it is shown that the bending moments are generally quite small and can be neglected for a simpler analysis.

Nanosecond pulsed electric fields cause melanomas to self-destruct

“…The tumor cells themselves also shrink over this time period because the cell density is higher by one and three hours post-treatment. The nuclear pyknosis that follows pulse application occurs faster than any previously observed pyknotic response [21] and may result from either electrodeformation [18] or the direct electric field interaction with cytoskeletal elements associated with the cell's nuclear lamina to generate the nuclear elongation and shrinking [22,23].…”

“…A typical tumor cell nucleus measuring 10 μm in diameter will experience a voltage gradient of about 40 V across itself during each pulse. This electric field is large enough to cause rapid electromechanical deformation of the nucleus [18,22] generating a mechanical shock to the DNA attached to the nuclear envelope that could damage the DNA.…”

“…A typical tumor cell nucleus measuring 10 μm in diameter will experience a voltage gradient of roughly 40 V across its diameter during each pulse. This electric field is large enough to cause electrodeformation [18]. …”

“…A typical tumor cell nucleus measuring 10 μm in diameter will experience a voltage gradient of about 40 V across itself during each pulse. This electric field is large enough to cause rapid electromechanical deformation of the nucleus [18,22] generating a mechanical shock to the DNA attached to the nuclear envelope that could damage the DNA.These nsPEFs stimulate murine melanomas to self-destruct by triggering rapid pyknosis and reducing blood flow without significant increases in caspase activity. A reduction in blood flow to tumors has also been observed following electrochemotherapy but does not occur until 24 h after treatment when the bleomycin entry had destroyed the endothelial cells [27].…”

Biomedical effects induced by the monocycle pulse

“…So, it is very critical to study the window effect of PEF on biological cells in order to precisely determine the PEF parameters and get effective therapeutic effects. The mechanism and threshold conditions of IEM have been extensively researched in the past few years (Lsambent, 1998;Chalise et al, 2006;Hu et al, 2009;Gurtovenko and Vattulainen, 2009;Pucihar et al, 2009;Sel et al, 2009;Hu et al, 2005;Joshi et al, 2002;Daniels and Rubinsky, 2009). Among the models and methods, an equivalent circuit method based on the multilayer dielectric model is popular to analyze the transmenbrane potential, the electric intensity threshold and the window effect.…”