"DNA glue" for self-assembly of three-dimensional structures
Three-dimensional nanostructures can be made using DNA glue
Kirill Stasevich, CompulentaUsing artificial DNA as a "programmable glue", it is possible to assemble 3D gel structures of a given shape up to 1 mm in size.
Our organs consist of functional units that fit exactly together – like, for example, lobes and segments of the liver. In turn, these functional units are formed due to the coordinated behavior of cells that connect to each other as they should, and not as they have to. We can say that a developing organ is a self–assembling structure, the program for the production of which consists in itself.
Researchers have been trying for a long time to reproduce the self-assembly processes taking place in the body so that it is possible to obtain a three-dimensional structure with predetermined properties. Such objects, composed of biological macromolecules or of some other biocompatible material, would come in very handy in tissue engineering, where one of the most difficult tasks is the creation of volumetric tissue structures.
The main question is how to program the building blocks so that they connect in the right way. When it comes to programming in biology, the first thing that comes to mind is DNA, whose molecule, as is known, consists of two chains that are held together due to the complementary coincidence of nucleotide sequences in each other. Researchers from Harvard (USA) eventually managed to create three-dimensional structures from DNA bricks that interacted with each other in a certain order and could form a number of spatial structures.
In a new paper published in Nature Communications (Qi et al., DNA-directed self-assembly of shape-controlled hydrogels), Peng Yin and his colleagues describe a modification of this method: gel cubes were used as building blocks, which were attached to each other using DNA fragments. As a matter of fact, at first scientists tried to assemble something from ordinary hydrogel cubes, but such blocks interacted with each other as they wanted, and eventually scientists figured out how to supply them with a construction program.
From a set of short DNA strands with a known sequence, a single long strand was made, which consisted of sections with a repeating sequence of nucleotides. Then it was wrapped around a cube of hydrogel: now it could only stick to a cube that was wrapped with DNA complementary to its own.
Diagram of the interaction of two gel cubes wrapped in complementary DNA strands
(here and below are illustrations by Peng Yin / Wyss Institute).However, the cubes themselves were only connecting elements: they were attached to larger blocks.
Small cubes with DNA now played the role of docking blocks for large "bricks", of which he became a part.
DNA served as a kind of cement mortar, or, as the authors themselves put it, a programmable glue, the program of which was a nucleotide sequence.
Scientists were able to assemble structures in this way in a wide range of sizes – from 30 microns to 1 mm. But the most important thing here is that structures with different linear parameters could be made from such elements: it was possible to make them into a chain, combine them into a large cube, make a T-shaped structure – everything depended on what kind of program the DNA glue would have and how the DNA gel docking elements would be located.
Formation of a programmed structure of several gel elements
with specific docking DNA gel cubes.
According to the authors of the work, this method can already be useful to those who are engaged in the cultivation of three-dimensional cellular structures. For example, such gel cubes may contain cells that, after the disappearance of the gel shell, will be next to each other in exactly the order that the researcher needs.
Prepared based on the materials of the Harvard Gazette: DNA glue directs tiny gel ‘bricks’ to self-assemble.
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