| This dissertation focuses on the study of polyelectrolyte systems through computational approaches. The research topics include scaling behavior of a single polyelectrolyte, DNA-templated self-assembly, and aggregation of biomolecules. The salt concentration dependence of the electrostatic persistence length of flexible polyelectrolytes has been the subject of extensive debate over the past two decades. Although theoretically a consensus has been reached regarding the correctness of the extension by Khokhlov and Khachaturian (KK) of the well-known Odijk-Skolnick-Fixman (OSF) theory to flexible polyelectrolytes, one crucial question remains: the strong disagreement between the OSF-KK prediction and various experimental observations. In Chapter 2, I perform extensive simulations of a flexible polyelectrolyte in solution to elucidate the origin of this discrepancy. Cationic-hydrophilic block copolymers have been developed as a potential carrier for gene delivery with good transfection efficiency and biocompatibility, where the cationic blocks can effectively condense the DNA into a core and the hydrophilic blocks can form a protective and stabilizing corona. Although the DNA condensation induced by the cationic block can be understood from energetic considerations, the formation of micelles with distinct morphologies is more complicated, as it involves several competing interactions. In Chapters 3 and 4, by correlating the simulation results with experimental observations, I investigate the interplay of various driving forces in the DNA-block copolymer self-assembly process and determine the key structural and experimental parameters influencing the morphology of the DNA-block copolymer micelles. Small interfering RNA (siRNA) therapeutics have a demonstrated potential for treating numerous genetically-related diseases. However, traditional polycation vectors used for siRNA delivery typically produce siRNA-containing particles of large size, high cytotoxicity, and low colloidal stability. In Chapter 5, along with my experimental collaborators, I report a new method to produce siRNA-containing nanoparticles with smaller sizes. The combination of experimental investigation and coarse-grained computer simulations suggest that the size reduction is achieved by breaking hydrogen bonding in the nanoparticles. |
