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Title: Understanding interactions between nanoparticles and lipid mesophases and their nanotoxicological significance
Author: Beddoes, Charlotte M.
ISNI:       0000 0004 5915 4290
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Understanding interactions between nano-objects and soft materials is important due to increasing usage of and consequent exposure to nanomaterials. Nanomaterials can infiltrate cells and inflict damage. However the mechanisms for the cellular ently by nanoparticles (NPs) are still not fully understood, and a better understanding is needed in order to predict how the physical parameters that characterise NPs can affect their cellular entry and impart subsequent cyto- and geno-toxicity. Previous experiments have focused on the qualitative and phenomenological observations from in vitro cell experiments. The aim of this project was to advance the current fundamental understanding of the processes related to nanotoxicity. In this work, lipids mesophases were used, to serve as simplified membrane models. The hypothesis was that lipid molecules undergoing mesophase transitions would experience the same elastic molecular deformations as those during endocytosis and membrane fusion, the process that underpins NP cellular entry. By varying the properties of the NPs such as size, surface chemistry and shape, their effects on lipid mesophases were analysed. The focus of this project is to shed light on how the presence of NPs could affect the energetic cost required for the transitions to take place between different lipid mesophases, which could be related to the more complex biological cells. Silica NPs were observed to increase the level of DNA damage for human choriocarcinoma placental BeWo b30 cells, however the tests could not fully account for the mechanisms which the silica NPs employed to cause the observed DNA damage. In an attempt to apply quantitative physicochemical methods to understand the physical mechanism of nanoparticle cellular entry lipids mesophases were used as a cell membrane model. Bare silica NPs of sizes of 3, 10, 25, 36 and 61 nm, 14 run polydimethylsiloxane (PDMS) coated hydrophobic silica NPs, and cellulose nanowhiskers (NWs) of 20 (diameter) x 200 (length) nm with surfaces bearing either of hydroxyl groups (neutral), anionic carboxylic acid groups, and cationic imiazole groups were added to monoolein mesophases. The mesophase structure and properties were determined from small angle X-ray and neutron scattering, in order to comprehend how the physical properties of the NPs affected the energy barrier for lipid deformations in the form of a mesophase transition.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available