Date on Master's Thesis/Doctoral Dissertation

5-2021

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemical Engineering

Degree Program

Chemical Engineering, PhD

Committee Chair

Jaeger, Vance

Committee Co-Chair (if applicable)

Fried, Joel

Committee Member

Fried, Joel

Committee Member

Gupta, Gautam

Committee Member

Walsh, Kevin

Author's Keywords

Molecular dynamics; electroporation; electric fields; cell membranes; nanopore structure; membrane properties

Abstract

Electroporation is a technique that induces the formation of open pores in cell membranes by the application of an electric field. Electroporation is widely practiced in research and clinical work for transfection of genetic sequences and drug molecule transport through the membrane barrier. However, a full theoretical explanation of the molecular mechanisms and thermodynamics responsible for pore formation, structure, and longevity does not yet exist. Advances in molecular dynamics simulations have enabled theoretical studies of electroporation with previously unobtainable fidelity spanning biologically relevant timescales. All-atom simulations utilizing the recently developed method of computational electrophysiology demonstrate that pore size correlates to the magnitude of the applied electric flux. This insight suggests improvements to electroporation protocols and instrument design to increase treatment efficacy while simultaneously decreasing cell mortality. Data processing, that scales and centers each simulation frame, generates a pore-centric matrix of voxels representing the time-averaged charge density of the simulation volume. This processing enabled the calculation of the first high resolution, three-dimensional maps of the electric fields that act to create and stabilize the pore. Applying this capability to individual moieties gives additional insight to how electrostatic forces between biomolecules and membrane structures give cell membranes their remarkable properties. Complementary processing of atom types, instead of partial charges, produces a similarly scaled, stabilized, and time averaged matrix of moiety number densities. Plotted in three dimensions, these density data reveal additional membrane structure detail that have not previously been reported.

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