Membrane proteins are involved in several fundamental biological processes such as transport or signal transduction. Most of them are enzymes, receptors or other important biological macromolecules representing up to 70% of therapeutic targets. Despite the interest in understanding their structures and behaviour the scientific knowledge is still very limited due to several practical difficulties. In 2009 a new platform for membrane protein studies called SMALP (Styrene-Maleic Acid Lipid Particles) nanodiscs was introduced. SMALPs are self-assembled structures formed by a bilayer of phospholipids controlled in diameter by a polystyrene maleic acid (SMA) copolymer belt. The purpose of this research project herein presented was to structurally characterise SMALPs, with analyses aimed to understand the role of both the polymeric and lipid parts in the self-assembly process. A series of investigations were carried out to elucidate the specific copolymer characteristics that allow the assembly into such well-defined, stable and reproducible structures. Experiments performed via small angle X-ray (SAXS) and neutron (SANS) scattering together with nuclear magnetic resonance (NMR), gel-filtration chromatography (GPC), dynamic light scattering (DLS), allowed identification of the specific polymeric characteristics of the copolymer architecture which were revealed to be crucial for the SMALPs assembly process. Investigations performed also addressed the question whether it was possible to assemble nanodiscs with the use of different phospholipids (with different chain length and charged or non-charged heads) and what the impact of the different lipids had on the structures. Finally, further analyses were made to test the physical chemical behaviour of the SMALPs when important environmental parameters such as temperature, pH and salt concentration of the buffer were changed.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:629677 |
| Date | January 2014 |
| Creators | Idini, Ilaria |
| Contributors | Edler, Karen ; Roser, Stephen |
| Publisher | University of Bath |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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