Molecular simulations of water and monovalent ion dynamics in the electroporation of phospholipid bilayers

Electroporation provides a controllable method to introduce foreign substances into living cells. It is widely used by researchers in cell biology and the medical field to manipulate biological systems at the cellular level. For decades, electroporation has been studied extensively through experiments and theoretical models, and electroporation-based technologies have been improved substantially with these efforts. One of the issues in utilizing electroporation is the lack of understanding in the phenomenon's molecular mechanism and the microscopic details, mainly due to the difficulty in the direct experimental observation of the nanosecond-scale electropore formation process and the nanometer-sized electropore structure. To overcome this issue, Molecular Dynamics (MD) simulation has become one of the major tools to study electroporation at the microscopic level.;Recent advancements of high performance computing, such as the increase in processing power, developments in algorithms and parallelization, have improved the efficiency of MD simulation substantially. Due to these advancements, MD simulation has become a popular tool for studying systems that are composed of biomolecules. For nearly a decade of effort, MD simulation revealed many different aspects of electroporation and it provided a molecular description of the process. Using MD simulation, we are able to observe the events during the electropore formation and annihilation, as well as the transport processes of molecules through the electropore. In addition, MD simulation provides a platform to study the molecular structure of electropore, and the associated energetic.;My dissertation is organized as the follows: Chapter 1 provides the motivation of this research by discussing the applications of electroporation-based technology, electroporation experiments, and the existing continuum model that describes electroporation. Chapter 2 introduces the MD formalism, models, and various algorithms used in our MD simulation. I will also discuss some of the previous MD studies of electroporation and their significances at the end of Chapter 2. In Chapter 3, we will examine the dynamics of water bridge during different stages of electroporation, and delineate the role of water molecules in electroporation by comparing the lipid bilayer system with an artificial water-vacuum-water system. In Chapter 4, we will examine the steady state of an electropore in lipid bilayer and evaluate the pore conductance of ions. The pore conductance values obtained from the simulations can be compared with those obtained by experiments. In Chapter 5, we will examine the effects that monovalent ions impose on lipid bilayer and electropore formation. We will also examine the pore conductance of ions under various ion concentrations, and the PS translocation process. At the end, I will summarize the findings in our research and provide a short outlook on MD simulation in the study of electroporation.