Rottensteiner, Alexia;
(2023)
DNA nanostructures for membrane probing and controlled poration.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
DNA nanotechnology excels at self-assembling structurally defined functional nanodevices. A recent avenue is to develop nanostructures that act at the bilayer interface to investigate or control membrane properties. The goal of this PhD is to create novel DNA nanostructures that probe and puncture lipid bilayers. Probing these bilayer properties is important for biophysical research and also for developing a diagnostic tool for various diseases such as cancer where circulating cancer cells express altered membrane elasticity compared to healthy cells. Currently, elasticity can be measured by tools such as atomic force microscopy (AFM) which is serial and requires specialised equipment. In comparison, the thesis describes a novel nanodevice built out of DNA, named DNA nanoactuator (NA), which binds to membranes and upon addition of single DNA strands deforms those membranes. The NA offers a highly parallel and simultaneous non-invasive analysis via fluorescence readout and broadens access to the nanodevice for any user of fluorescence microscopy. Aside from membrane probing, this PhD project features a DNA valve for controllable membrane poration. Nanochannels are the most relevant border crossings in nature but their application is restricted due to the complicated introduction of wide-ranging modifications in their structure and function. A broadened structural range can be attained with DNA as building materials for nanochannels. To expand their function, a light trigger for controlled opening and closing and tuneable membrane transport was constructed. Photoswitchable azobenzene molecules were incorporated into the DNA nanochannel to control duplex dissociation for channel opening and closing. The light-gated pore allows precise design, quick assembly, and easy, non-invasive activation. The pore can find applications in artificial cell systems and for targeted drug delivery. In conclusion, the proposed DNA nanostructures advance the field of DNA nanotechnology and present new routes to understand membranes or alter their permeation properties for basic and applied science.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | DNA nanostructures for membrane probing and controlled poration |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10172724 |
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