Bottom-up Fabrication of Functional DNA Nanostructures
Abstract: This thesis demonstrates bottom-up fabrication of a fully addressable non-repetitive network on the nanometer scale, assembled by synthetic DNA molecules. Each side constitutes a unique sequence of 10 bases, i.e. 3.4 nm in length, and can be considered the smallest practical unit of DNA in a nanotechnological context. Working with units of this length scale ensures a system fit for non-mundane molecular nanotechnology. The thesis features a progressive growth of the nanostructure, from the formation of the single-ringed hexagonal unit-cell to an asymmetric four-ring network of 17 nodes. Each structure is formed in a one-step self-assembly reaction. Alongside construction of the DNA-based nanostructural template, the thesis also illustrates three different aspects of functionalization. Firstly, a fixation strategy infusing stability in the delicate network by chemical ligation. The click chemistry based strategy will pave the way for modular build-up of larger nanostructures. Results show that multiple site-specific click reactions can perform simultaneously and independently of each other on a hybridized DNA template. Fixated modules are resistant to denaturing agent and can be freeze-dried. The second important aspect is incorporation of these DNA nanoconstructs onto lipid bilayers, for development of soft-surface nanotechnology. This creates controllable new interfaces in an aspiration towards membrane-integrated applications, e.g. mimicking a photosynthetic reaction centre. This thesis features two different molecular anchors: a multi-functional porphyrin moiety and a more universal lipid anchor. Both anchors are shown to align a DNA nanostructure with the membrane surface, a conformational arrangement that also depends on position of anchoring points. The last theme of this thesis is triplex recognition as a method for site-specific functionalization of preformed DNA nanostructures. The specific function of energy transfer is demonstrated in a simple photonic device, which can be switched ON and OFF by slight adjustment of pH. This DNA-based nanoscopic system is envisioned as a platform for high-precision control over molecular processes towards nanotechnological applications. It is part of an ambition in molecular nanoscience to fabricate systems from the bottom-up, based on principles of self-assembly and with functional complexity on levels not achievable by a conventional top-down perspective to nanoscience. The great leap of molecular nanoscience stems from inspiration of biological systems. New advancement in technological progress is possible by harvesting benefits of Darwinian evolution.
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