Meng, Zhuojun

English

Grote inzet is toegewijd aan het gebruik van DNA als bouwsteen in de nanotechnologie door zijn veelzijdige eigenschappen, zoals hoge specificiteit en programmeerbaarheid om complexe structuren te vormen. In dit proefschrift hebben wij door middel van hydrofobe eenheden aan de nucleobasen te bevestigen een nieuwe strategie vastgesteld voor het verankeren van oligonucleotiden in vesikelmembranen en aangetoond dat chemische synthese een waardevol hulpmiddel is om functionele DNA moleculen te produceren om de complexiteit van membraan-aanpassingsmethoden te verhogen. Nadat de stabiliteit van lipide-DNA in de vesikelmembranen was aangetoond, werd lipide-DNA geïnduceerde vesikelfusie bestudeerd. Er werd bevonden dat de oriëntatie van DNA hybridisatie en het aantal verankeringseenheden een cruciale rol speelden bij vesikelfusie. Om de functionaliteit van DNA-gebaseerde vesikels verder uit te breiden, werd de hybridisatie en dynamische uitwisseling van DNA op het oppervlak van liposomen onderzocht door toevoeging van DNA sequenties. Verder werd een DNA-gebaseerd amplificatieproces uitgevoerd op het oppervlak van liposomen met een DNA-probe. Ten slotte hebben wij met succes de prestatie van een DNA-gemedieerd amplificatieproces op de zebravishuid aangetoond. Door de brede toepassing van zebravis als diermodel in de ontwikkeling van geneesmiddelen, toxicologie en nanodeeltjes karakterisatie in levende systemen, geloven wij dat het hier gepresenteerde platform de combinatie van DNA-nanotechnologie met levende dieren in staat stelt en efficiënte bio-barcoding en in vivo tracking mogelijk maakt.Great efforts have been dedicated to use DNA as a building block in nanotechnology because of its versatile properties, such as high specificity and programmability to form complex structures. In this thesis, we have established a new strategy for anchoring oligonucleotides in vesicle membranes enabled by attaching hydrophobic units to the nucleobase and shown that chemical synthesis is a valuable tool to produce functional DNA molecules to increase the complexity of membrane engineering approaches. After demonstrating the stability of lipid-DNA in the vesicle membranes, lipid-DNA induced vesicle fusion was studied. It was found that the orientation of DNA hybridization and the number of anchoring units played a crucial role in vesicle fusion. To further extend the functionality of DNA-based vesicles, we explored the hybridization and dynamic exchange of DNA on the surface of liposomes by simple addition of DNA sequences. Moreover, a DNA based amplification process was performed on the surface of liposomes with a DNA probe. Finally, we successfully demonstrated the performance of a DNA mediated amplification process on the zebrafish skin. Due to the broad application of zebrafish as animal model in drug development, toxicology and nanoparticles characterization in living systems, we believe the platform presented here allows amalgamation of DNA nanotechnology tools with live animals and enables efficient bio-barcoding as well as in vivo tracking

ARTS repository - University of Groningen

   University of GroningenDNA nanotechnology as a tool to manipulate lipid bilayer membranesMeng, ZhuojunIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2017Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Meng, Z. (2017). DNA nanotechnology as a tool to manipulate lipid bilayer membranes. [Thesis fullyinternal (DIV), University of Groningen]. University of Groningen.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 13-02-2023       DNA nanotechnology as a tool to manipulate lipid bilayer membranes     Zhuojun Meng            DNA nanotechnology as a tool to manipulate lipid bilayer membranes   Zhuojun Meng PhD thesis University of Groningen  October 2017  Zernike Institute PhD thesis series 2017-22 ISSN: 1570-1530 ISBN: 978-90-367-9976-8 (printed version) ISBN: 978-90-367-9975-1 (electronic version)  The research described in thesis was carried out in Polymer Chemistry and Bioengineering group at Zernike Institute for Advanced Materials, University of Groningen, The Netherlands. This work was financially supported by the Chinese Scholarship Council (CSC), the University of Groningen and the Netherlands Organization for Science Research (NWO).                      Cover design by: Zhuojun Meng Printed by: Ridderprint BV        DNA nanotechnology as a tool to manipulate lipid bilayer membranes       PhD thesis   to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus Prof. E. Sterken and in accordance with the decision by the College of Deans.  This thesis will be defended in public on   Friday 13 October 2017 at 16.15 hours  by  Zhuojun Meng born on 5 May 1987 in Henan, China     Supervisor Prof. A. Herrmann    Assessment committee Prof. S. Vogel Prof. A. M. van Oijen Prof. D. J. Slotboom              Dedicated this book to myself and my best friend  Qing Liu             Contents  Chapter 1 Functionalization of Lipid Bilayer Membranes ......................................................... 9 1. 1 Lipid bilayer membranes ................................................................................... 10 1.2 Classification and Preparation of Liposomes .............................................. 12 1.3 Modification and Applications of liposomes ............................................... 14 1.4 Motivation and Thesis Overview ...................................................................... 24 References ......................................................................................................................... 26  Chapter 2 Stability Study of Lipid-DNA on the Liposomal Membrane ............................... 31 2.1 Introduction .............................................................................................................. 32 2.2 Results and Discussion ......................................................................................... 35 2.3 Conclusion ................................................................................................................. 42 2.4 Experimental Section ............................................................................................ 42 References ......................................................................................................................... 48  Chapter 3 Efficient Fusion of Liposomes by Nucleobase Quadruple-Anchored DNA .. 51 3.1 Introduction .............................................................................................................. 52 3.2 Results and Discussion ......................................................................................... 54 3.3 Conclusion ................................................................................................................. 63 3.4 Experimental Section ............................................................................................ 65 References ......................................................................................................................... 69      Chapter 4 DNA Replacement and Hybridization Chain Reaction on the Surface of Liposome Membrane ......................................................................................................... 73 4.1 Introduction .............................................................................................................. 74 4.2 Results and Discussion ......................................................................................... 76 4.4 Experimental Section ............................................................................................ 84 References ......................................................................................................................... 88  Chapter 5 Performing DNA Nanotechnology Operations on a Zebrafish Surface ......... 91 5.1 Introduction .............................................................................................................. 92 5.2 Results and Discussion ......................................................................................... 94 5.3 Conclusion ................................................................................................................ 101 5.4 Experiment Section .............................................................................................. 103 References ....................................................................................................................... 105  Summary ............................................................................................................................. 108 Samenvatting .................................................................................................................... 114 Acknowledgements ....................................................................................................... 119     

DNA nanotechnology as a tool to manipulate lipid bilayer membranes

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DNA nanotechnology as a tool to manipulate lipid bilayer membranes

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