Towards an understanding of the self-assembly and applications of phospholipid-containing nanoparticles

Hall, Stephen Christopher Lewis ORCID: 0000-0003-0753-5123 (2019). Towards an understanding of the self-assembly and applications of phospholipid-containing nanoparticles. University of Birmingham. Ph.D.

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Abstract

Polymer-stabilized phospholipid nanodiscs are nanoscale, discoidal assemblies containing a central core of lipid bilayer stabilized in aqueous solution by an amphipathic copolymer belt. Recently, nanodiscs have been applied to the extraction of membrane proteins directly from cellular membranes. However, the rapid adoption of nanodisc technology for biomolecular studies has outpaced the communities understanding of the fundamental properties of nanodisc-forming polymers which influence nanodisc self-assembly, as well as the inherent properties of the nanodiscs themselves.
In this study, the thermodynamics of nanodisc self-assembly have been probed in order to gain insights into the structural properties of existing and novel polymers which affect the self-assembly process. Subsequently, their application to solubilisation of biological membranes has been investigated, overcoming limitations of the current technology. Following these studies, investigations into the interaction of nanodiscs with pre-existing membranes at interfaces were performed, revealing how lipid exchange kinetics vary between nanodisc types. Furthermore, polymer-stabilised nanodiscs were observed to adsorb to lipid bilayers, enabling future surface-based studies of nanodisc-encapsulated membrane proteins. Finally, polymer-stabilized nanodiscs were shown to provide a soluble membrane surface for investigation of protein-lipid interactions. This has revealed a membrane-induced fibrilization of the bacterial lipoprotein YraP, providing clues as to its currently unknown function.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):