Date on Master's Thesis/Doctoral Dissertation
Chemical Engineering, PhD
Committee Co-Chair (if applicable)
Molecular dynamics; electroporation; electric fields; cell membranes; nanopore structure; membrane properties
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.
Brian, Joseph Patrick P.E., "Mapping three dimensional interactions between biomolecules and electric fields." (2021). Electronic Theses and Dissertations. Paper 3584.