Molecular Interactions between Nanoparticles and Model Cell Membranes Investigated by Sum Frequency Generation Vibrational Spectroscopy.

It is important to understand the interactions between nanoparticles (NPs) and cells because the use of NPs as nanomedicines requires the NPs to enter the target cells in order to reach subcellular organelles. For the cellular entry of NPs, it remains unclear how the cell membrane molecules respond to the NPs due to a lack of appropriate surface/interface-sensitive techniques to study these NP-cell membrane interactions in situ in real time. In this thesis, sum frequency generation (SFG) vibrational spectroscopy was applied to examine the molecular interactions between lipid bilayers (serving as model mammalian cell membranes) and NPs with different sizes, surface chemistry, and nature. It was found that both Au and Ag NPs could induce lipid flip-flop for the model membranes. Flip-flop is an important biological process in which the lipid molecules translocate from one leaflet to the other. Such a process is essential to maintain the cell membrane asymmetry which is strongly associated with cell functions and cell apoptosis. The lipid flip-flop rate was found to increase as the Au NP size increased with respect to the same particle number or the same NP surface area. However, the induced lipid flip-flop rate was independent of mass, which was interpreted by the same “effective surface contact area” between Au NPs and the model cell membrane. For NP surface chemistry effect, it was found a higher surface coverage of carboxyl functional groups on Au NPs tends to induce faster lipid flip-flop. For amine functionalized NPs, a slower interaction rate was found in most cases for NPs with a higher surface coverage. Au NP solution pH also influences Au NP – lipid bilayer interactions. Additionally, Ag NP-model cell membrane interaction was also investigated. Ag NPs induce slower lipid flip-flop of the model cell membrane than Au NPs. The accumulation and possible aggregation of Ag NPs on cell membrane could also be observed. This research laid a foundation to investigate molecular interactions between NPs and model cell membranes using SFG. SFG can characterize the molecular behaviors of NPs with each leaflet of the lipid bilayer during the NP-model cell membrane interaction in situ.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135918/1/peiphu_1.pd