DNA Sequence and Length Dictate the Assembly of Nucleic Acid Block Copolymers

Abstract

The self-assembly of block copolymers is often rationalized by structure and microphase separation; pathways that diverge from this parameter space may provide new mechanisms of polymer assembly. Here, we show that the sequence and length of single-stranded DNA directly influence the self-assembly of sequence-defined DNA block copolymers. While increasing the length of DNA led to predictable changes in selfassembly, changing only the sequence of DNA produced three distinct structures: spherical micelles (spherical nucleic acids, SNAs) from flexible poly(thymine) DNA, fibers from semirigid mixed-sequence DNA, and networked superstructures from rigid poly(adenine) DNA. The secondary structure of poly(adenine) DNA strands drives a temperature-dependent polymerization and assembly mechanism: copolymers stored in an SNA reservoir form fibers after thermal activation, which then aggregate upon cooling to form interwoven networks. DNA is often used as a programming code that aids in nanostructure addressability and function. Here, we show that the inherent physical and chemical properties of single-stranded DNA sequences also make them an ideal material to direct self-assembled morphologies and select for new methods of supramolecular polymerization.

Solution-Phase Synthesis of DNA Amphiphiles for DNA Micellar Assembly

“…The method allows convenient synthesis of amphiphilic DNAs with various DNA sequence, length, modification location, and modification identity. This development, we believe, would facilitate detailed investigation of amphiphilic DNA assembly, which could be important for drug delivery and nanoconstruction. ,− …”

“…The DNAs used in this study include polythymine, poly­(T), and scrambled DNA sequences. In principle, the DNA sequence may influence the amphiphilic ssDNA assembly morphology, but not broadly explored here. After modification, the amphiphilic ssDNA was named as T x -PS Sy -C n +1 for poly­(T) and SS x -PS Sy -C n +1 for the scrambled DNA sequences.…”

A General Signal Amplifier of Self-Assembled DNA Micelles for Sensitive Quantification of Biomarkers

“…The DNA micelle (DM) is self-assembled from amphiphilic molecules which are composed of hydrophilic DNA strands and hydrophobic monomers. 11 Since the driving force for this assembly is hydrophobic effects 12 and does not depend on DNA base pairing, rigorous sequence design is not required. In addition, thanks to the discovery that the G-quadruplex effectively stabilized the DM structure, 13,14 its application in diagnosis is more extensive.…”

“…The DNA micelle (DM) is self-assembled from amphiphilic molecules which are composed of hydrophilic DNA strands and hydrophobic monomers . Since the driving force for this assembly is hydrophobic effects and does not depend on DNA base pairing, rigorous sequence design is not required.…”

Programming Aggregate States of DNA Nanorods with Sub-10 nm Hydrophobic Patterns for Tunable Cell Entry

“…Recently, a number of rigid amphiphilic DNA nanostructures have been created via decorating hydrophobic moieties on DNA frameworks. These structures have been employed to interact with lipid membranes for a range of applications, such as the construction of synthetic transmembrane receptors, nanopores, and nanochannels, − the assembly of DNA superstructures on lipid layers, − the shaping − and reshaping , of lipid structures with defined geometries, and the rewiring of intercellular connections. , On the other hand, amphiphilic DNA nanostructures can form micelle-like aggregates under proper conditions via hydrophobic interactions in aqueous solutions. − According to several recent studies, − amphiphilic DNA nanostructures are more effective at entering cells than plain ones, but the correlation between their aggregate states and cell entry efficiency is yet to be explored.…”