Characterizing & modelling the bio-nano interface
Author(s)
Belessiotis Richards, Alexis
Type
Thesis
Abstract
The rise of nanotechnology has to led numerous developments in the fields of biotech- nology and medicine. The promise of nanoparticles delivering drugs in vivo and nano- materials peering into cells are highly sought after and currently investigated in research groups around the world. However, despite the potential of such technologies, much is still unknown about the interface between these materials and the biological world. This thesis aims to further our understanding of this interface in order to aid the design of future generations of materials with new and improved functionality.
Coarse-grained molecular dynamics simulations were employed to study how nanoporous surfaces can affect model cell membranes in close contact. This modelling showed that curvature can be induced in membranes by fine-tuning nanoporous surfaces leading to preferential local changes in membrane properties and preferential localization of pro- teins. This model was expanded to study in further detail the membrane binding and cur- vature sensing of a key curvature-active protein domain, the Epsin N-Terminal Homology (ENTH) domain. This protein was shown to be able to sense membrane curvature with- out its terminal H0 amphipathic helix both with and without the presence of its key lipid binding partner, phosphatidylinositol 4,5-bisphosphate (PIP2). In addition, another PIP2- binding, curvature-active protein, the AP180 N-Terminal Homology (ANTH) domain, was investigated with this modelling system in order to evaluate the curvature-sensitivity of the domain with three different terminal helix compositions. This domain was shown to have innate curvature sensitivity on neutral membranes. In the presence of PIP2 however, only the fully rigid helix structure allowed for curvature sensing of this protein.
In addition to modelling approaches to understand the bio-nano interface, x-ray photo- electron spectroscopy (XPS) was employed to characterize the surfaces of nanostrutured silicon surfaces in order to understand their surface chemistry for biological applications. Gold nanoclusters (AuNCs) were also studied in order to explore the nature of catalytic reactions occurring on their surface.
Coarse-grained molecular dynamics simulations were employed to study how nanoporous surfaces can affect model cell membranes in close contact. This modelling showed that curvature can be induced in membranes by fine-tuning nanoporous surfaces leading to preferential local changes in membrane properties and preferential localization of pro- teins. This model was expanded to study in further detail the membrane binding and cur- vature sensing of a key curvature-active protein domain, the Epsin N-Terminal Homology (ENTH) domain. This protein was shown to be able to sense membrane curvature with- out its terminal H0 amphipathic helix both with and without the presence of its key lipid binding partner, phosphatidylinositol 4,5-bisphosphate (PIP2). In addition, another PIP2- binding, curvature-active protein, the AP180 N-Terminal Homology (ANTH) domain, was investigated with this modelling system in order to evaluate the curvature-sensitivity of the domain with three different terminal helix compositions. This domain was shown to have innate curvature sensitivity on neutral membranes. In the presence of PIP2 however, only the fully rigid helix structure allowed for curvature sensing of this protein.
In addition to modelling approaches to understand the bio-nano interface, x-ray photo- electron spectroscopy (XPS) was employed to characterize the surfaces of nanostrutured silicon surfaces in order to understand their surface chemistry for biological applications. Gold nanoclusters (AuNCs) were also studied in order to explore the nature of catalytic reactions occurring on their surface.
Version
Open Access
Date Issued
2021-04
Date Awarded
2021-08
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Stevens, Molly
Sponsor
Engineering and Physical Sciences Research Council
Grant Number
EP/L015277/1
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)