Framework Nucleic Acids Mediated Biomineralization

Biomineralization is the process by which an organism generates inorganic minerals through the regulation of biomolecules.The most significant difference from general mineralization is the presence of biomolecules,metabolism,cells and organic matrix.Biomineralization can produce a variety of inorganic minerals,such as silica,calcium carbonate,calcium phosphate and magnetic iron oxide.The resulting biominerals generally have hierarchical and ordered structures of various sizes with excellent mechanical properties that perform far beyond that of their artificial counterparts.For example,the silica minerals in the diatom shell have intricately hierarchical porous structure and provide excellent mechanical support and protection for the diatom cells.Therefore,it is urgent to simulate biomineralization reaction to construct advanced functional materials with similar properties in vitro.However,up to now,the mineral materials constructed from bottom-up strategy using biological organic molecules are far from the complex and ordered structures of biological minerals spanning nanometer to micrometer.DNA,as the important genetic material of life,has derived the powerful DNA nanotechnology.With a variety of design strategies and computer aided techniques,DNA nanostructures with a variety of morphologies can be accurately constructed on nanometer to micron or even millimeter scales.The molecular recognition between nucleic acids and the mineral counterparts can be facilitated by the electrostatic interaction between the DNA phosphate backbone and the cationic molecule/ions.Therefore,customized designer framework nucleic acids are ideal candidates to use as structural frameworks/templates to direct the growth of biominerals in a controllable and programmable fashion.This dissertation systematically analyzed how to use framework nucleic acids to encode the nanoscale biomineralization with prescribed design.The main research content is as follows:(1)A new idea of using framework nucleic acid as organic molecular template to construct biomaterial with specific morphology and size was proposed.A kind of multihole framework nucleic acid with micron size and honeycomb pattern was designed and synthesized by imitating the structure of silica in diatom shell,which provided an ideal template for the accurate reconstruction of silica in diatom shell in vitro.At the same time,various framework nucleic acid templates with multiple structures were constructed successively,laying a foundation for the precise control of the synthesis of mineral nanoparticles.(2)A general approach to create DNA-silica hybrid nanostructures,called DNA origami silicification(DOS),was presented by constructing pre-hydrolyzed clusters to deposit silica onto the surface of DNA surface.Through the analysis of DOS structure,it is proved that this method can replicate the morphological features of DNA nanostructures at the nano level,and the construction of DNA-silica nanopores with the pore size less than 5 nm is realized.The general fabrication of DOS is proved by creating various DOS architectures,such as frame-like,curved and porous DNA nanostructures,with one to three-dimensional and complex hierarchical architectures.By templating inorganic materials using designer DNA nanoobjects,this DNA-based mineralization strategy represents a new tool for highly programmable nanofabrication.(3)Next,this dissertation studied the nanomechanical properties of these DOS nanoobjects and gave a quantitative description of the solidifying function of silica.We found these DOS architectures showed improved rigidity,while maintaining flexible mechanical features owing to organic-inorganic components.After establishing a robust membrane substrate effect correction(MSEC)model,we found the compressing Young's modulus(E-modulus)of DOS structure has an increase in one order of magnitude as compared to its original DNA template,which proved that its mechanical properties were significantly improved.Finally,the construction of a DNA-metal-silica composite with stable configuration indicates that silica can provide excellent support and protection for nano-biological materials.(4)Last,this DOS idea was expanded to another biomineral-calcium phosphate(Ca P)nanocrystal and a DNA framework templated Ca P crystallization strategy was developed to guide the mineralization of Ca P nanocrystals with prescribe shapes.The morphology of thus-produced Ca P nanocrystals generally followed the designed topology of DNA frameworks with high accuracy.By controlling the three-dimensional morphology of the framework nucleic acid,the crystal form of Ca P nanocrystals can be controlled.The tetrahedral Ca P nanocrystals had typical twin crystal structure,while the triangular Ca P nanocrystals had apex-center asymmetric crystal structure.Further,the synchrotron-based small angle X-ray scattering(SAXS)and molecule dynamics(MD)simulation were employed to elucidate the template crystallization mechanism of Ca P.In summary,this dissertation provided a fundamental and general strategy for constructing mineralized nanostructures by using functional framework nucleic acids as templates,which opened up a new path for bottom-up nanotechnology.