General Strategy for the Design of DNA Coding Sequences Applied to Nanoparticle Assembly

Abstract

The DNA-directed assembly of nano-objects has been the subject of many recent studies as a means to construct advanced nanomaterial architectures. Although much experimental in silico work has been presented and discussed, there has been no in-depth consideration of the proper design of single-strand sticky termination of DNA sequences, noted as ssST, which is important in avoiding self-folding within one DNA strand, unwanted strand-to-strand interaction, and mismatching. In this work, a new comprehensive and computationally efficient optimization algorithm is presented for the construction of all possible DNA sequences that specifically prevents these issues. This optimization procedure is also effective when a spacer section is used, typically repeated sequences of thymine or adenine placed between the ssST and the nano-object, to address the most conventional experimental protocols. We systematically discuss the fundamental statistics of DNA sequences considering complementarities limited to two (or three) adjacent pairs to avoid self-folding and hybridization of identical strands due to unwanted complements and mismatching. The optimized DNA sequences can reach maximum lengths of 9 to 34 bases depending on the level of applied constraints. The thermodynamic properties of the allowed sequences are used to develop a ranking for each design. For instance, we show that the maximum melting temperature saturates with 14 bases under typical solvation and concentration conditions. Thus, DNA ssST with optimized sequences are developed for segments ranging from 4 to 40 bases, providing a very useful guide for all technological protocols. An experimental test is presented and discussed using the aggregation of Al and CuO nanoparticles and is shown to validate and illustrate the importance of the proposed DNA coding sequence optimization.

Covalent and Non‐Covalent DNA–Gold‐Nanoparticle Interactions: New Avenues of Research

“…On the other hand, AuNPs are noted by its potential non‐cytotoxicity, even if recent publications have reported on conflicting data on their toxicity . Besides, interactions of other nanoparticles (NPs) such as silver, metal oxides, graphene oxides, or Al and CuO with DNA have been recently described, gold colloids are arguably the most stable among metal NPs suspensions …”

“…[5] On the other hand, AuNPs are noted by its potential non-cytotoxicity, [6] even if recent publications have reported on conflicting data on their toxicity. [7] Besides, interactions of other nanoparticles (NPs) such as silver, [8,9] metal oxides, [10] graphene oxides, [11] or Al and CuO with DNA have been recently described, [12] gold colloidsa re arguably the most stable among metal NPs suspensions. [13,14] It is important to note that NPs are characterizedn ot only by the properties of the metal cluster core but also by the organic molecules that protect the colloid from aggregation and constitute the monolayer,t hat is, the capping agents.…”

DNA Grafting and Arrangement on Oxide Surfaces for Self-Assembly of Al and CuO Nanoparticles

“…This temperature is sufficient to ensure a de-hybridization of complementary strands, as demonstrated previously by studying the thermal behavior of Al-CuO nanocomposites under 70 °C, 34 (reported in SI Figure S3). However, this temperature is believed not to release oligonucleotides directly grafted on the nanoparticle surface, i.e.…”

“…However, the hybridization between specifically grafted complementary DNA oligonucleotides is dominant compared to non-specific interactions in the overall self-assembly process, as previously demonstrated. 34 Briefly, aggregation kinetics and SEM images of the self-assembled composites obtained with or without complementary DNA strands are presented in SI Figure S7. Table S8.…”

“…In our second work, we showed that the DNA "sticky-end" sequence has a strong effect on the efficiency of strand hybridization involved in the self-assembly process, demonstrating a significant improvement of the homogeneity of the final structure of the composite. 34 We further investigate the bio-functionalization of Al@Al 2 O 3 and CuO nanoparticles by performing, for the first time, a complete characterization of streptavidin and DNA grafting densities and hybridization efficiency on nanoparticles. The objectives of this work are to: (i) quantify streptavidin and DNA oligonucleotides coverages, (ii) optimize basic experimental parameters such as salt concentration, incubation time and degree of sonication (usually studied for gold nanoparticles) to maximize DNA loading, and (iii) determine the specificity of grafted DNAs, and quantify their concentrations and their resulting ability to hybridize to a complementary strand.…”