Date of Award

Summer 2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical & Computer Engineering

Committee Director

Ravindra P. Joshi

Committee Member

Linda L. Vahala

Committee Member

Juergen Kolb

Committee Member

Duc T. Nguyen

Abstract

This dissertation research focuses on the new field of pulsed electric field interactions with biological cells. In particular, "Intracellular Electromanipulation" which has important biomedical applications, is probed. Among the various aspects studied, nanosecond, high-intensity pulse induced electroporation is one phenomena. It is simulated based on a coupled scheme involving the current continuity and Smoluchowski equations. A dynamic pore model can be achieved by including a dependence on the pore population density and a variable membrane tension. These changes make the pore formation energy E(r) self-adjusting and dynamic in response to pore formation. Additionally, molecular dynamics (MD) simulations are also discussed as a more accurate, though computationally intensive, alternative.

Besides inducing pores in cells, external voltages could also be used, in principle, to modulate action potential generation in nerves. The electric-field induced poration could block action potential propagation. This aspect has been studied by modifying the traditional cable model for nerves, by accounting for the increased membrane conductance and the altered membrane capacitance. This conduction block in nerves due to an electroporation related local short-circuit would be similar in concept to stopping the propagation of an air-pressure wave down a "leaky" pipe.

This study also focuses on threshold process in cellular apoptosis induced by nanosecond, high-intensity electric pulses. In particular, the pulse number dependent cell survival trends are quantified based on a biophysical model of the cellular apoptotic processes. Time-dependent evolution of the caspase concentrations and the various molecular species are simulated. The numerical evaluations provide qualitative predictions of pulse number cell survival, the relative assessment of extrinsic and intrinsic pathways, and rough predictions of the time duration over which irreversible activation at the molecular level could be initiated by the electric pulses. Time dependent kinetics of the caspases as well as the various molecular species within the apoptotic pathway, were simulated using the rate equation model originally proposed by Bagci et al.

Finally, an asymmetric electroporation model is presented. Electric pulsing pore energy and mechanical pore energy are studied. This has relevance to the flow of ions in and out of cells.

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DOI

10.25777/x81z-qe88

ISBN

9781124291543

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