Patches for nanotubes
Broken DNA nanotubes patched up holes in themselves with spare parts
Alexander Dubov, N+1
American biochemists have obtained nanotubes from DNA, which independently restore the structure destroyed by interaction with nucleases. To do this, spare DNA elements capable of attaching to the damaged area were added to the medium with nanotubes. This approach makes it possible to four times slow down the destruction of artificial nano- and microstructures based on DNA in enzyme-rich biological media, scientists write in Nano Letters (DNA Nanostructures that Self-Heal in Serum).
Nucleic acid molecules contain four types of nitrogenous bases in their composition, which can bind to each other in pairs, connecting two different polymer chains. The principle of such pairwise correspondence – complementarity – is used by living organisms to synthesize new molecules, encode and transmit information, and by biochemists and materials scientists to create artificial nanostructures of a given shape based on DNA or RNA. In particular, it is on this principle that the DNA origami technique is based, with the help of which it is now possible to obtain three-dimensional structures of a given shape from DNA weighing up to several hundred megadaltons. Due to the fact that it is quite easy to attach other biopolymers or inorganic particles to DNA, the range of possible applications of these structures is quite wide: this includes the creation of molecular computers, the production of nanosensors, and the delivery of drugs inside the body.
One of the problems of such artificial structures based on DNA is not very high stability in enzyme–rich biological environments in which these nano- and micro-materials are going to be actively used (for example, for drug delivery and cancer therapy). Thus, in the serum solution of a calf embryo (a typical model medium for biochemical studies), unprotected DNA nanostructures do not live more than a day. As a rule, in such cases, to protect artificial DNA structures, they are either covered with a protective membrane, or another substrate for nuclease is added to the medium, which it will destroy instead of the structure that you want to preserve. These methods, however, are either too complex or severely limit the functionality of the DNA structures themselves.
Biochemists Yi Li and Rebecca Schulman from Johns Hopkins University has proposed another way to solve this problem. It turned out that it is not necessary to try to somehow influence the interaction of DNA with nuclease by adding protective shells and occupying it with something else, you can simply increase the concentration of building blocks in the medium (short sections of DNA from which the nanotube itself is built).
The structure of one building block ("monomer") and the DNA nanotube obtained from such blocks. Drawings from the article in Nano Letters.
Initially, from such blocks connected to polyethylene glycol molecules, the nanotube itself is formed with a length of several micrometers and fixed on a glass substrate. After that, the nanotubes are placed in a serum rich in various enzymes, including nucleases, which hydrolyze the phosphodiester bond and thus destroy the DNA structure. According to theoretical models, if the same building blocks that make up the DNA nanotube are additionally added to this medium as "spare parts", the growth rate can be higher than the hydrolysis rate, which increases the lifetime of the nanotube.
Aging of DNA nanotubes in the serum solution of the calf embryo (left) and in the same solution, but with the addition of additional DNA building elements (right).
Scientists were able to detect such an effect experimentally. It turned out that when additional building blocks are added to the serum, the destruction of the nanotube under the action of enzymes slows down, its lifetime increases almost fourfold. The fluorescence microscopy data confirmed the mechanism of "self-fixing" of nanostructures and showed that this really happens precisely due to the embedding of new blocks into the tube structure. At the same time, an additional effect is associated with the fact that DNA monomers in solution serve as an alternative substrate for nucleases and also reduce their activity with respect to nanotubes.
Fluorescent micrographs of DNA nanotubes fixed on a glass substrate in their original state and after repair. The pieces of the initial nanotube are shown in blue, those added after repair are green, the "seed" for self–assembly of the nanotube is red.
According to the authors of the work, a similar effect is observed for larger DNA-based microstructures. Biochemists claim that in the near future their proposed method (possibly combined with alternative ways to slow down the chemical destruction of DNA nanostructures in biological media) can be used for in vivo research and the development of specific medical applications.
Recall that artificial nano- and microstructures based on DNA are proposed to be used not only for medical purposes. For example, American researchers a few years ago proposed using DNA molecules as an electromechanical switch. In another work, biochemists used a DNA structure as a robotic arm, which, under the influence of an electric field, is able to move molecules or nanoparticles by several tens of nanometers in just a few milliseconds. In addition, artificial structures from DNA are also proposed to be used as a matrix for obtaining inorganic particles, which can then be used as elements of optical sensors.
Portal "Eternal youth" http://vechnayamolodost.ru