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Hybrid nanosystems fabricated by molecular recognition

Liu, Juan. Hybrid nanosystems fabricated by molecular recognition. 2015, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_11289

Abstract

The cell can be viewed as a miniature factory run by a large collection of molecular machines such as proteins and DNA that works together to perform complicated tasks, such as cell division, response to environmental stimuli, and energy production. Currently, nanotechnology research aims at reconstructing a fraction of complex functionality that exists in cell by designing novel systems to mimic cell properties and functions. The design of hybrid nanosystems based on biomacromolecules such as proteins, DNA, and synthetic molecules (polymers), brings science closer to achieving this target. The adaptability and mechanical properties of polymers allow for tailored designs that include various scaffolds for improved spatial-temporal connections to specific proteins, and DNA.
In this thesis, two hybrid systems were established. First, tris-nitrilotriacetic acid (trisNTA) functionalized polymers (PNTs) for the specific conjugation of his-tagged molecules was designed and synthesized. For efficient binding to the His-tagged molecules, a chelating metal (Me2+) is introduced in the trisNTA site. The binding affinity of His-tagged molecules for the trisNTA-Me2+, and their interactions when bound were analyzed. These characteristics were dependent on the distance between the trisNTA binding sites and the size of his-tagged molecules. In addition to the distance between trisNTA binding sites on PNTs, the nature of the selected Me2+, connecting trisNTA and His tag, offers a way to tune the binding affinity of the protein for the polymer, and in this way the protein-protein interactions can also be modified to further tune the stability of the conjugates and their susceptibility to release under changing pH. The concept of polymers serving as models for combined geometric topology with size requirements is expected to show the real binding capacity of molecules to a complex targeting configuration, mimicing biological systems in details. In addition, PNTs fulfill the requirements as a great nanocarrier for protein delivery and can contribute to the development of protein therapy and other protein-related applications.
Second, we applied DNA as the algorithm to regulate the self-organization of binary polymersomes to construct multicompartmentalized structures with spatial organization and connections. Polymersomes supply a robust and shielded encapsulation of active entities, while DNA is capable to control the spatial organization and the spatial distance between compartments due to the rigid nature of double-strand DNA (<50 nm). The size of polymersomes as the second algorithm plays an important role in the assembly behavior and results in different architectures, including linear and satellite structures. The compartmentalized polymer network system described in this work offers a new perspective into the evolution from unitary (one component) to binary (two components) or polyphyletic (multiple components) systems with properties greater than the individual building blocks.
Advisors:Meier, Wolfgang Peter
Committee Members:Nardin, Corinne
Faculties and Departments:05 Faculty of Science > Departement Chemie > Chemie > Makromolekulare Chemie (Meier)
Item Type:Thesis
Thesis no:11289
Bibsysno:Link to catalogue
Number of Pages:157 p.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:57
Deposited On:29 Jun 2015 09:04

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