DNA scaffolds for functional hydrogels

Change log

DNA scaffolds self-assembled by short-stranded synthetic DNA can be tailored to build thermally reversible hydrogels with target binding sites. These hydrogels exhibit highly selective binding properties due to the specificity of DNA and also provide an aqueous environment for various reactions to happen within the network constraints. Hence, a careful study on the assembly mechanism and other physical aspects of DNA hydrogels is required to facilitate the future design and construction of such materials at the precise control.

In this thesis, I present the work on well-designed DNA nano-stars as scaffolds for functional bulk materials with potential applications in bio-sensing.

Chapter 1 starts with introducing the fundamental properties of DNA molecules, focusing on the advantages of utilising short-stranded DNA to programme and engineer micro- and macro- materials. Then it briefly reviews the field of rheology and micro-rheology, with the diffusing wave spectroscopy (DWS) technique illustrated explicitly as an example passive micro-rheology tool. Afterwards, a critical literature review on computational modelling of DNA systems is present, followed by the thesis outline at the end.

Chapter 2 describes a simple DNA dendrimer system self-assembled from three-armed DNA nano-stars. The characterisation tools such as UV-vis spectroscopy, gel electrophoresis and dynamic light scattering (DLS) are introduced to verify the final production of the complex DNA structures. From this practice, we develop a routine for designing DNA scaffolds that yield optimal productivity.

Chapter 3 investigates the mechanical properties of DNA hydrogels made of three-armed DNA nano-stars and how they change upon cooling and heating empolying DWS micro-rheology. The resulting viscoelastic moduli over a broad range of frequencies reveal a clear, temperature-reversible percolation transition coinciding with the melting temperature of the system's sticky ends. This indicates that we can achieve precise control in mechanical properties of DNA hydrogels, which is beneficial for designing more sensitive molecular sensing tools and controlled release systems.

Chapter 4 develops a coarse-graining computational model of DNA hydrogels that resembles the system in Chapter 3 using LAMMPS, a classical molecular dynamics code. Thermodynamics, structural analysis and rheology tests were taken, qualitatively reproducing the physical phenomena of DNA assembly of the hydrogel network.

Chapter 5 studies the internal behaviours of three-armed DNA complexes using oxDNA model also implemented in LAMMPS, with particular focus on the effect of the inert bases in the core and between double-stranded branches and single-stranded sticky ends. A deep insight into sequence-dependent behaviour of such complex structures can guide the parameter optimisation of the individual building blocks for the model described in Chapter 4.

Chapter 6 concludes the thesis and presents an outlook for the future work that emerged out of my experimental and numerical studies.

Eiser, Erika
Y-shaped DNA, DNA hydrogels, microrheology, molecular dynamic simulations
Doctor of Philosophy (PhD)
Awarding Institution
University of Cambridge
National University of Defense Technology, China