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Title: Polymer theory applied to the nuclear pore complex
Author: Osmanovic, D.
ISNI:       0000 0004 5358 9074
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Physically interesting behaviour can arise when soft matter is confined to nanoscale dimensions. A highly relevant biological example of such a phenomenon is the Nuclear Pore Complex (NPC), found perforating the Nuclear Envelope of all eukaryotic cells. In the central conduit of the NPC, of 30-60 nm diameter, a disordered arrangement of proteins regulates all macromolecular transport between the nucleus and the cytoplasm. Its selectivity for larger macromolecules relies on changes in a permeability barrier that is formed by these unstructured proteins, induced by interactions of these proteins with molecules called Nuclear Transport Receptors (NTRs), which can chaperone larger macromolecules through the NPC. The exact mechanism for the transport selectivity is unknown. To model these unstructured proteins in the nanoscale channel of the NPC, a density functional theory approach is developed that treats the proteins as interacting polymers. This new method is tested against Monte Carlo to show its validity. A detailed comparison between this model system and those previously proposed in the literature is provided. In a parameter range relevant for the NPC, the system shows bimodal behaviour The polymers can alternate between two condensed states: An open state, in which this condensation takes place at the channel wall, and a closed state in which it occurs at the channel centre. We then extend this model by including explicitly the effect of Nuclear Transport Receptors on the conformations of the polymers. The model takes into account the finite size of the transport receptors relative to the NPC diameter. Mapping the polymer and transport receptor behaviour over a set of physiologically relevant parameters gives different structural scenarios for the various hypothesized transport mechanisms. Further to this, the transport rates for each parameter set can be obtained, showing whether such parameters are consistent with experimental evidence. In addition to this, we study the effect of relaxing some of the assumptions of our model, specifically by looking at azimuthal symmetry breaking effects in two dimensions. We also compare our model to experimental results measuring the thickness of planar polymer brushes comprised of NPC proteins to further justify parameter choices.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available