Bio-Inspired Concepts: Studies of Biological Response to External Electric Fields for Cellular Manipulation and Diagnostics - Modeling and Experimentation

摘要

A comprehensive modeling and experimental effort was carried out to develop an understanding of cellular bio-response to short duration, high-intensity electric fields. Macroscopic models for determining the time-dependent spatially-variable electric potential and current flows at single cells were developed. This provides predictions of both transmembrane voltages and temperature changes. The macroscopic model was coupled to a nano-simulator to probe the sub-cellular response at the molecular level. Many of the observed details such as PS externalization, the time scales for pore formation, and their probable diameters were predicted. The relevant parameters of the bio- system were obtained within our group by developing the Time Domain Dielectric Spectroscopy method. The system is operational, and yields data on the conductivity and permittivities of cells and its organelles. This is a useful and important development. Cellular responses were measured based on a variety of techniques, including flow cytometry, optical microscopy and imaging. The central results were: (i) There is a critical electric field and pulse duration for cell death; (ii) The critical voltage reduces for multiple pulses and increases pulse width; (iii) PS externalization leading to cell death can be electrically triggered; and (iv) Pore formation can be reversible for short nano-second pulses. This study would be indicative of the following conclusions: (i) It may be energy efficient to use short pulses for cell death; (ii) Selective apoptotic targeting of cells appears to be possible; and (iii) Non-uniform internal potentials (arising from dipole and charge placements) promote cellular transport. Hence, their modification/disruption through molecular conformational change would alter cell functioning.