The assembly and structure of self-assembling peptides: molecular to supramolecular

Morris, Kyle (2012) The assembly and structure of self-assembling peptides: molecular to supramolecular. Doctoral thesis (PhD), University of Sussex.

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Abstract

Self-assembling molecules are central to a plethora of processes found in nature, biotechnology
and even disease. The importance of the non-covalent interaction of monomers to the formation
of fibrillar assemblies is evident in the repeated use of this mechanism throughout nature, from
essential cellular processes such as the formation of the cytoskeleton to the production of silk.
Further, it has been recognised in the last two decades that a self-assembly mechanism, that is
the formation of amyloid, underpins the pathology of protein misfolding diseases; it is therefore
essential to dissect these mechanisms.

Despite recent technological and model system developments, self-assembling molecules
remain challenging to investigate. Using combined structural and biophysical characterisations
of penta- and hexa-peptide self-assembling model systems these investigations shed further
light on the structure of amyloid-like fibrils. The elucidation of the structures of these fibrillar
systems not only has implications for disease but also makes them well placed for consideration
for biotechnological applications.

In reflecting upon how cross-ß structural architectures can be organised in the fibrillar state, a
molecular and supramolecular model of fibrils formed by a fragment of !-synuclein is reported.
The fibrils are found to consist of a novel and elaborate cross-ß architecture that leads to a
helical supramolecular assembly spanning length scales previously unobserved for such a
system.

Where self-assembly is a useful route to supramolecular structure formation, the use of low
molecular weight gelator (LMWG) peptides to create fibrillar structures with defined material
properties is also explored. The complex link between molecular structure, self-assembled
architecture, fibril formation, fibril interaction and ultimately bulk material properties is
described. It is found that the determinants of self-assembly are distinct from the determinants
of gelation and so future LMWG design will have to consider both individually.

This work presents methodological advances in the characterisation of self-assembled structures.
The investigations presented here have relevance for disease related processes but also to the
technological use of these systems as materials. Finally, this work emphasises the beauty of the
extravagant, yet elegant connection between molecular interaction and supramolecular selfassembly.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Library Cataloguing
Date Deposited: 29 Jun 2012 05:58
Last Modified: 29 Jun 2016 07:54
URI: http://sro.sussex.ac.uk/id/eprint/39707

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