Polymer stabilised phospholipid nanodiscs – Protein: polymer interactions
: (Alternative Format Thesis)

  • Kerrie Morrison

Student thesis: Doctoral ThesisPhD


Membrane proteins play fundamental roles in the regulation of biological processes in cells and organisms. They have many responsibilities, such as signalling and transport of substances across lipid bilayers. Additionally, they provide targets for around 70 % of pharmaceutical drugs.
Although membrane proteins are known for their importance, there is a distinct deficit in their structural and functional characterisation. This bottleneck of information is caused by a number of reasons, such as their fragility and ability to degrade and mis-fold. In 2009, a new method was developed to extract these proteins from membranes, utilising the copolymer poly (styrene-co-maleic acid) (SMA), creating nanodiscs to support membrane protein extraction. In the past
decade, more copolymers have been developed to counteract limitations of the original SMA; many membrane proteins have also been studied using this technique, and overall structural characterisation of the nanodisc formation has been further investigated. Yet, there is little information on the interactions occurring within the nanodisc, with limited studies exploring membrane
protein activity in nanodiscs.

The initial purpose behind this research was to investigate the protein-polymer interactions within the nanodisc, by examining protein functionality using two different proteins. This in turn would provide a platform to screen newly synthesised copolymers, to determine their success in extracting membrane proteins, which maintain their natural functionality. However, the findings
spurred on additional lines of enquiry, focussing on particular physical aspects of membrane proteins documented to be successfully extracted in literature, and comparing them to those deemed less successful. Further study using mass spectroscopy (MS) proteomics has provided a global insight into potential preferential extraction when comparing SMA to control extracted samples. Lastly, further study into structural characterisation of membrane proteins
that have been incorporated into nanodiscs has been investigated. This study used a combination of different techniques; circular dichroism (CD), dynamic light scattering (DLS), small angle neutron scattering (SANS) and ab initio modelling constructs to gather structural information on the protein and nanodisc formation, comparing these methods to others, such as protein
crystallography. These findings highlighted the differences between various techniques and the importance of using complementary methods to fully determine nanodisc structures. Overall, this thesis emphasises the complexity of the protein-nanodisc system and introduces potential factors to consider when using this technique, such as protein-polymer interactions.
Date of Award14 Feb 2022
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorKaren Edler (Supervisor), Paul Whitley (Supervisor), Gareth Price (Supervisor) & James Doutch (Supervisor)


  • SMALPs
  • nanodisc
  • SMA

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