Dissertation/Thesis Abstract

Design, investigation, and application of nucleic acid architectures
by Koyfman, Alexey Yuri, Ph.D., University of California, Santa Barbara, 2008, 160; 3342062
Abstract (Summary)

DNA is used in nature as a biological material of choice to store and transfer genetic information. RNA can fold into intricate three dimensional structures utilizing a number of naturally occurring structural motifs, and is used for enzymatic catalysis, and gene expression and regulation. Both nucleic acids are promising in bionanotechnology due to their defined length, unique base pair recognition capabilities, and possible base and backbone modifications.

RNA squares were constructed through the use of four unique kissing loop-loop interactions incorporated in four monomers. Unique six nucleotide single stranded overhangs were positioned on the 3’ end of each monomer in order to assemble RNA squares into linear and 2D patterns, visualized using atomic force microscopy (AFM). Visual and computer analysis of the AFM two-dimensional array data resulted in two distinct orientations of 2D RNA domains.

Linear arrangement of cationic gold nanoparticles can be directed by one dimensional RNA ladders. Regular spacing of nanoparticles is controlled by the RNA architectures acting as scaffolding. Thus, precise positioning of molecular components can be accomplished with RNA through electrostatics and via size and shape recognitions.

However, four unique single-stranded overhangs at each corner of an RNA unit often limit the well-ordered domain size to less than micron sizes. By introducing identical and symmetrical single-stranded DNA overhangs large, isotropic two dimensional DNA architectures that extend across several microns were generated. We describe the self-assembly of multilayer hexagonal DNA arrays through highly regular inter-layer packing. Slow cooling of a mixture of three single-stranded DNA sequences with various Mg2+ concentrations leads to the self-assembly of diverse multilayer architectures.

Specific attachments of hexagonal DNA arrays to tumor cells using two different methods are illustrated. This DNA system can be used to specifically deliver a number of small molecules to cells, selectively label certain cells and organize cellular assemblies.

An emerging challenge for bionanotechnology is to create defined architectures with highly addressable subunits that can be used in electronics, sensors and medicine. Nucleic acids provide a route to achieve this, although the factors which control the assembly processes are still being identified.

Indexing (document details)
Advisor: Reich, Norbert O.
Commitee: Safinya, Cyrus R., Sagermann, Martin, Samuel, Charles E.
School: University of California, Santa Barbara
Department: Biomolecular Science and Engineering
School Location: United States -- California
Source: DAI-B 70/01, Dissertation Abstracts International
Subjects: Biochemistry
Keywords: Nucleic acids, RNA squares, Self-assembly
Publication Number: 3342062
ISBN: 9780549988915
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