Kinetic Trans-Assembly of DNA Nanostructures

Abstract

The central dogma of molecular biology is the principal framework for understanding how nucleic acid information is propagated and used by living systems to create complex biomolecules. Here, by integrating the structural and dynamic paradigms of DNA nanotechnology, we present a rationally designed synthetic platform that functions in an analogous manner to create complex DNA nanostructures. Starting from one type of DNA nanostructure, DNA strand displacement circuits were designed to interact and pass along the information encoded in the initial structure to mediate the self-assembly of a different type of structure, the final output structure depending on the type of circuit triggered. Using this concept of a DNA structure "trans-assembling" a different DNA structure through nonlocal strand displacement circuitry, four different schemes were implemented. Specifically, 1D ladder and 2D double-crossover (DX) lattices were designed to kinetically trigger DNA circuits to activate polymerization of either ring structures or another type of DX lattice under enzyme-free, isothermal conditions. In each scheme, the desired multilayer reaction pathway was activated, among multiple possible pathways, ultimately leading to the downstream self-assembly of the correct output structure.

Development and functionalization of DNA nanostructures for biomedical applications

“…However, double crossover (DX) tiles consisting of two DNA duplexes with swap chains created at two distinct points, resulted in stiffness values that were twice as high as linear DNA (Figure 1). 18 This finding led to the creation of triple crossover (TX) models to design stiffer cross‐shaped motifs or 4–12 helix knots acting as the spiral beams, and tensegrity triangular tiles 4,12 . The polymerization of these diverse motifs gave rise to stable nano‐ribbon lattices and nanotubes with periodic patterns 19 .…”

“…Such stable motifs were evaluated for polymerization into patterned structures without the conventional B‐conformation of DNA 11 . Similarly, the isothermal toehold‐based strand displacement approach was introduced as a tool to design highly stable DNA nanostructures using extensive computational modeling approaches 12 . Effective bio‐responsive behavior was attained to formulate a variety of programmable sensors, nano‐devices, and nano‐robots after functionalization with fluorophores, gold nanoparticles (AuNPs), and ligands for bioanalysis of cellular events, and in vivo targeting to release payloads 9,13 .…”

Supermolecular Nanoentities of Vitamin B12 Derivative as a Link in the Evolution of the Parent Molecules During Self-Assembly at the Air–Water Interface

“…Vitamin B 12 and its derivatives, together with many other important biomolecules in supramolecular assemblies, possess an impressive variety of functional properties which are used in natural systems performing their vital functions in living organisms. − Nanostructures of numerous biomolecules, having different properties from those of the parent molecules and with great potential for various applications have been previously reported. − However, to date, there have been no reports of nanostructures of vitamin B 12 (biomolecule of porphyrin-type) and its derivatives.…”

High Reactivity of Supermolecular Nanoentities of a Vitamin B12 Derivative in Langmuir–Schaefer Films Toward Gaseous Toxins

“…Nowadays, nanostructures of numerous biomolecules having different properties from those of the parent molecules and with great potential for various applications have been reported. , Self-assembly is a key player in material nanoarchitectonics, − the nanostructures formed in this way arising from molecules carrying side groups that promote the process. Supramolecular polymers have been created using diverse self-assembly strategies. , The formation of different kinds of molecular assemblies from precursor compounds at the water surface has been reported. , We previously demonstrated the possibility of supramolecular design at the air–water interface by controlling the self-assembly of tetrapyrrole compounds into 2D and 3D nanostructures. − The concept of nanostructuring of organic compounds at the air–water interface and a model of a floating layer, the structural units of which can be both individual molecules (Langmuir’s approach, special case) and their major nanostructures (so-called M-nanostructures, general case), were presented. − The formation of the porphyrin supermolecules from magnesium porphine, a functional element of chlorophyll, was reported …”