DNA Binding to Gold Nanoparticles through the Prism of Molecular Selection: Sequence–Affinity Relation

Native
DNA strongly adsorbs to citrate-coated gold nanoparticles
(AuNPs). The resulting composites (DNA/AuNPs) are valuable materials
in many fields, especially in biomedicine. For this reason, the process
of adsorption is a focus for intensive research. In this work, DNA
adsorption to gold nanoparticles was studied using a molecular selection
procedure followed by high-throughput DNA sequencing. The chemically
synthesized DNA library containing a central N26 randomized
fragment was sieved through four cycles of adsorption to AuNPs in
a tree-like selection-amplification scheme (SELEX (Selective Evolution
of Ligands by EXponential enrichment)). The frequencies of occurrence
of specific oligomeric DNA motifs, k-mers (k = 1–6), in the initial and selected pools were
calculated. Distribution of secondary structures in the pools was
analyzed. A large set of diverse A, T, and G enriched k-mers undergo a pronounced positive selection, and these sequences
demonstrate faster and strong binding to the AuNPs. For facile binding,
such structural motifs should be located in the loop regions of weak
intramolecular complexeshairpins with imperfect stem, or other
portion of the structure, which is unpaired under selection conditions.
Our data also show that, under the conditions employed in this study,
cytosine is significantly depleted during the selection process, although
guanine remains unchanged. These regularities were confirmed in a
series of binding experiments with a set of synthetic DNA oligonucleotides.
The detailed analysis of DNA binding to AuNPs shows that the sequence
specificity of this interaction is low due to its nature, although
the presence and the number of specific structural motifs in DNA affect
both the rate of formation and the strength of the formed noncovalent
associates with AuNPs.