Microdosimetric Realistic Model of a Cell with Endoplasmic Reticulum.

When investigating the biophysical effects induced by the interaction between electromagnetic fields and biological cells, it is crucial to estimate the electromagnetic field intensity at the microscopic scale (microdosimetry). This information allows to find a connection between the external applied field and the observed biological event required to establish related biomedical applications. Here, authors present a microdosimetric study based on a 2D realistic model of a cell and its endoplasmic reticulum. The microdosimetric analysis of the cell and endoplasmic reticulum was quantified in terms of electric field and transmembrane potential induced by an externally applied high amplitude 10-ns pulsed electric field. In addition, electroporated local membrane sites and pore densities were also evaluated. This study opens the way to numerically assist experimental applications of nanosecond pulsed electric fields for controlled bio-manipulation of cells and subcellular organelles.

A microdosimetry study for a realistic shaped nucleus.

In the last decades, the effects of ultrashort pulsed electric fields have been investigated demonstrating their capability to be involved in a great number of medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). In particular, experiments in literature demonstrate that internal structures can be involved when pulse duration is reduced. Up to now, the mechanism that permits the electroporation phenomenon has not been completely understood and hence atomistic, microdosimetry and dosimetry models have been developed to help in this field. Aim of this work is to demonstrate the importance of realistically model also the internal organelles to obtain predictive results of effects at sub-cellular level with a microdosimetry model.

Microchambers for cell exposure: from the design to applications.

In the last decades, the advances in the micro and nano fabrication techniques have led to the development of microdevices that improved the possibility of analysis at cell level. These devices can be used in different applications (e.g., cell detection and identification, manipulation, cell treatments). The requisites, that are necessary to achieve, are different for various applications and represent the starting point of the project. The numerical multiphysics models can be very advantageous to analyze the performances of such devices and to predict their operation. Aim of this work is to give a look of the design rules of microchamber devices in particular for their application in electric field exposure. Two different applications for cell discrimination and characterization are reported considering time and frequency domain measurements.

Novel passive element circuits for microdosimetry of nanosecond pulsed electric fields.

Microdosimetric models for biological cells have assumed increasing significance in the development of nanosecond pulsed electric field technology for medical applications. In this paper, novel passive element circuits, able to take into account the dielectric dispersion of the cell, are provided. The circuital analyses are performed on a set of input pulses classified in accordance with the current literature. Accurate data in terms of transmembrane potential are obtained in both time and frequency domains for different cell models. In addition, a sensitivity study of the transfer function for the cell geometrical and dielectric parameters has been carried out. This analysis offers a new, simple, and efficient tool to characterize the nsPEFs' action at the cellular level.

Effects of nanosecond pulsed electric fields on the activity of a Hodgkin and Huxley neuron model.

The cell membrane poration is one of the main assessed biological effects of nanosecond pulsed electric fields (nsPEF). This structural change of the cell membrane appears soon after the pulse delivery and lasts for a time period long enough to modify the electrical activity of excitable membranes in neurons. Inserting such a phenomenon in a Hodgkin and Huxley neuron model by means of an enhanced time varying conductance resulted in the temporary inhibition of the action potential generation. The inhibition time is a function of the level of poration, the pore resealing time and the background stimulation level of the neuron. Such results suggest that the neuronal activity may be efficiently modulated by the delivery of repeated pulses. This opens the way to the use of nsPEFs as a stimulation technique alternative to the conventional direct electric stimulation for medical applications such as chronic pain treatment.

Signal transduction on enzymes: the effect of electromagnetic field stimuli on superoxide dismutase (SOD).

Protein functions and characteristics can highly differ from physiological conditions in presence of chemical, mechanical or electromagnetic stimuli. In this work we provide a rigorous picture of electric field effects on proteins behavior investigating, at atomistic details, the possible ways in which an external signal can be transduced into biochemical effects. Results from molecular dynamics (MD) simulations of a single superoxidismutase (SOD) enzyme in presence of high exogenous alternate electric fields will be discussed.