Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Computational and Molecular Biophysics


English (en)

Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Nathan Baker


Perfluorocarbon based nanoemulsion particles: PFC-NEPs) are very small sized: ~ 250 nm in diameter) greasy droplets that are enclosed by emulsifying phospholipid monolayer. PFC-NEPs have been extensively developed for target-specific delivery of therapeutic agents such as imaging agents and drug molecules. Because of the extremely small sizes of PFC-NEPs and fluid nature of their surface, the structure of these particles at atomic resolutions has yet to be determined by experimental approaches. The aim of this thesis is to determine the atomistic structure of PFC-NEP interfaces with a particular focus on their interaction with model target bilayers. The goal of this work is to help understand the molecular mechanisms for PFC-NEP cargo binding and delivery. Such understanding will enable the rational design of PFC-NEPs for optimal delivery and eventually lay a foundation to customize the particles for delivery of specific cargo molecules. To achieve this goal, we have used molecular dynamics: MD) simulations at both atomistic and coarse-grained levels using in-house force field parameters developed for a perfluorocarbon molecule that forms the emulsion core. By employing atomistic simulations, the PFC-NEP interface structure was determined in the absence and presence of a model cargo. The interface structure featured the intercalation of the PFC molecules into the emulsifying monolayer and differential cargo binding to the PFC-NEP interface as a consequence of the intercalation, which expressed the need to modulate the level of mixing of PFC with the emulsifying monolayer for cargo binding to PFC-NEPs. Coarse-grained MD simulations have been employed to test a proposed hemifusion mechanism for PFC-NEP delivery of cargo to target bilayers. Our simulations showed that PFC-NEP and liposome particles fused after encounter; distinct molecular details were observed from the fusion mechanism between two bilayers. This thesis research has not only provided the detailed structure to elucidate molecular mechanisms for cargo binding and delivery but also laid a foundation to decipher the correlation between the structure and function of PFC-NEPs for more systematic studies in the future.


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