3D DNA origami as precise building blocks in protocellular systems

Abstract: Nature creates intelligent systems by encoding functionality through hierarchical self-assembly, in which sensing and signaling is coupled to responsive, dynamic behavior. This complex orchestration in time and space is summed up in biological cells, which are seen as the smallest living entity. For decades, research has aimed at understanding both their structure and function as well as mimic complex cell behavior. Simple cell mimics, termed protocells, aim to replicate and orchestrate cellular functions such as compartmentalization and spatiotemporal assembly.
While the underlying forces of static self-assembly in plain solution are well understood, engineering of protocellular components remains challenging. Moreover, going from static to dynamic assemblies, we still lack control over transient structures, which are an integral part of cellular behavior. Further spatiotemporal control is necessary for replication of truly dynamic self-assembly by engineering systems that are able to sense and adapt via internal feedback loops.
In this thesis, I develop three systems as protocellular components to gain insight into the underlying assembly principles and engineer highly modular systems, which are able to mimic key features of cellular behavior. For this purpose, I employ DNA origami, a scaffolded DNA assembly approach for highly compact and stable DNA nanostructures, which I use as building block in all of my systems.
To begin with, I concentrate on enabling molecular flux across protocellular membranes. For this purpose, I rationally design DNA origami nanopores equipped with hydrophobic anchors for the generation of polymersome protocells with the ability for compartmentalization and controlled membrane permeability.
The cytoskeleton is another important cell feature for transport and cell movement. It consists of highly organized filamentous structures, which reconfigure on demand. As protocellular cytoskeleton components, I design 1D nanotubes able to polymerize from single DNA origami nanocylinders. The polymerization is fully reversible by responding to an external DNA antifuel trigger and repeated cycles of (de)polymerization are successfully implemented.
Finally, I couple these nanotubes to a chemical reaction network to replicate the transient behavior of cytoskeleton filaments. For this purpose, I use a second origami, a nanocuboid monomer able to communicate with the nanocylinder via a complex set of DNA strand displacement reactions. After polymerization of nanocylinders to nanotubes a negative feedback causes a delayed depolymerization to yield a dynamic system of transient nanotubes

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2021

Klassifikation und Themen

• Schlagwort: Building ; DNS-Origami ; Assembly

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Gröer, Saskia
• Beteiligte Personen und Organisationen: Walther, Andreas ; Albert-Ludwigs-Universität Freiburg. Fakultät für Chemie und Pharmazie

Weitere Informationen

• DOI: 10.6094/UNIFR/194843
• URN: urn:nbn:de:bsz:25-freidok-1948436
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:38 MESZ