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Title: Designing self-assembled, functional mesocompartments utilising molecular interactions
Author: Williams, David J.
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2012
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The central themes of this thesis are the design aspects and function of versatile molecular assemblies that mimic the behaviour of biological compartments, such as the cell. Synthetic biomimetic compartments are designed by utilising specific molecular interactions, which direct self-assembly. Coacervates, formed by spontaneous liquid-liquid phase separation upon ionic assembly of polyelectrolytes, have been described as a novel phase of soft matter. For the first time, nucleotide small molecules (the building block of nucleic acids) have been employed in the formation of coacervate droplets through facile mixing with the polycation, poly(diallyldimethylammonium) chloride (PDDA). Coacervate formation has been shown to be dependent upon the strength of the ionic interaction between the polyvalent anion and polycation. Moreover, this novel nucleotide-based coacervate is highly stable, existing in the form of microscopic droplet dispersions in aqueous solution that are capable of sequestering chemical species, such as organic dyes, porphyrins, biopolymer-coated inorganic nanoparticles and proteins. Supramolecular assembly of porphyrin molecules and enhanced enzyme activity within the coacervate droplets has been demonstrated, highlighting the function of such a material as a biomimetic compartment. Building upon initial work, the high molecular weight polymer PDDA has been replaced with lower molecular weight poly(L-lysine) (PLys) in order to produce coacervate microdroplets using biologically-relevant components. Such nucleotide- peptide coacervate droplets are of particular interest in the search for plausible routes towards a model protocell. A wide range of nucleotide molecules (including di- and mono-phosphate species) and the redox cofactor flavin adenine dinucleotide (FAD) have been employed as coacervate building blocks. Using 24 or 3 kDa PLys coacervate droplets were formed with the characteristic stability and uptake properties previously observed. Nanoparticle or enzyme mediated catalysis within the droplets was achieved and intra-droplet porphyrin aggregation demonstrated. Finally, self-assembled nanostructures were formed using a biomimetic peptide sequence covalently tethered to a phospholipid tail. Discrete, micellar aggregates were identified, characterised and shown to preferentially solubilise hydrophobic molecules and, through ionic preorganization, could be encapsulated within a nanoscopic biomineral shell.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available