Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.723020
Title: Directing the self-assembly of short peptide derivatives
Author: Conte, Maria Paola
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2017
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Abstract:
Self-assembly of molecular building blocks has attracted increasing interest as an effective bottom-up approach for the design of functional nanomaterials. Amongst the variety of known molecular building blocks, very short (di- and tri-) peptides and their derivatives are of particular relevance in this context due to their chemical simplicity, low cost and remarkable properties. In this thesis, we first investigate the behaviour of the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) in a predominantly aqueous environment. We demonstrate that these molecules can form metastable hydrogels upon a combination of solvent switching and sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel. Thanks to the highlyhydrophobic nature of the fibres formed, the gels can be employed as selective scavengers for small hydrophobic molecules. Combining biocatalysis and molecular self-assembly provides an effective approach for processing of self-assembled materials, directing the assembly kinetics by means of catalysis which results in the controlled formation of hierarchical nanostructures. Herein, we investigate the possibility to achieve localised self-assembly of peptide derivatives exploiting different strategies to immobilize enzymes, thereby adding spatial control over the self-assembly process. We functionalised surfaces with bioinspired polydopamine and polyphenol coatings to study the effects of enzyme surface localisation and surface release on the self-assembly process. We demonstrate how these coatings could be conveniently used to release protease enzyme thermolysin into a pre-gelator (Fmoc-T and F-NH2) solution for bulk gelation as well as to irreversibly immobilize the enzyme for localizing the self-assembly to the surface. Enzyme-(magnetic)nanoparticle conjugates were employed to trigger the self-assembly and gelation of peptide derivatives in two different systems, an equilibrium system and a far from equilibrium one. For both systems, the self-assembly results in the formation of stable hydrogels. We were able to visualise the self-assembled nanostructures at the site of enzyme immobilization by electron microscopy. Moreover, employing magnetic nanoparticles allows for an additional level of control on the properties of the hydrogels, which can be manipulated with an external magnetic field. Finally, we employed a soft-lithographic technique (microcontact printing) to transfer a pattern of enzymes onto a modified substrate. The surfaces with the patterned thermolysin were used to trigger the localized formation of the gelator Fmoc-TF-NH2 through direct condensation of two non-assembling precursors Fmoc-T and F-NH2. Fluorescence microscopy was employed to confirm the localized formation of self-assembled structure by staining the β-sheet fibres with Thioflavin T. The thesis concludes with a number of overall conclusions that can be drawn from the work presented, as well as some possible directions for future work.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.723020  DOI: Not available
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