02 February 2022

Dice game

Researchers use microscopic DNA strands to assemble hydrogel blocks

Nonna Mikhailova, HLEB

Researchers from Okinawa University of Science and Technology (OIST) used microscopic DNA strands to guide the assembly of gel cubes visible to the naked eye. Scientists report that hydrogel blocks up to 2 mm in size, containing DNA on their surface, self-assemble in about 10-15 minutes when mixed with a solution.

Dr. Vyankat Sontake, the first author of the study and a researcher in the Department of Chemistry and Engineering of nucleic acids of OIST: "We think that these blocks of hydrogel are the largest objects that have been programmed by DNA to form structured structures."

The article by Vyankat A. Sontakke and Yohei Yokobayashi Programmable Macroscopic Self-Assembly of DNA-Decorated Hydrogels is published in the Journal of the American Chemical Society.

The process of self-assembly, in which an organized structure is spontaneously formed by the interaction of two or more individual components, is so common in nature that cells and DNA can self-assemble into surprisingly complex microscopic structures. But the use of interactions occurring at the molecular level to control the assembly of macroscopic objects (in the sense of visible to the naked eye) is a relatively new field of research, especially in the field of DNA.

"We chose DNA because it is well programmed and owes its remarkable ability to recognize sequences," said senior author Professor Yohei Yokobayashi, who heads the department of chemistry and engineering of nucleic acids.

Double-stranded DNA consists of two single strands of DNA that twist around each other to form a double helix. The threads are fastened by interweaving the bases, which are connected to each other like a zipper (A with T and C with D). This specific ability to pair bases means that scientists can create strands of DNA that exactly match other chains and will bind to each other.

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Drawings from the press release of OIST Scientists use 'sticky' DNA to build organized structures of gel blocks.

In one experiment, researchers attached single-stranded DNA molecules to the surface of red and green hydrogel blocks. The DNA strands on the red blocks are complementary to the DNA strands on the green blocks.

When the hydrogel blocks are shaken in solution, the corresponding DNA strands join together, acting as the "glue" that holds the red and green blocks together. After ten minutes, the separated blocks independently assemble into a simple branching structure of alternating colors.

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It is important to note that the DNA strands did not interact with identical DNA strands on other blocks, so the hydrogel blocks of the same color did not stick together.

The scientists also tested the ability of DNA to recognize only certain sequences by creating four pairs of matching chains. They attached individual carriers of the first matched pair to the surface of the red cubes of hydrogel. The same process was performed for green, blue and yellow hydrogel cubes.

When shaken, despite the presence of many different DNA sequences, the strands bind only to the corresponding strand, resulting in the formation of previously mixed blocks of hydrogel, which self-split into clusters of the same color.

Professor Yokobayashi said: "This shows that the self-assembly process is very specific and can be easily programmed. By simply changing the DNA sequence, we can control the blocks so that they interact with each other in different ways."

In addition to self-assembly, the researchers also studied whether they could use DNA to program the disassembly of the structure. They created two identical single strands of DNA, and then made a third, shorter strand that matched part of the first. They attached the first thread and the same shorter thread to the hydrogel cubes, which self-assemble when mixed in solution. Then a longer DNA strand matching the first strand was added to the solution, and within an hour the longer strand displaced the shorter one, as a result of which the cubes unraveled.

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"This is really exciting because it means that by using DNA as the 'glue' to glue together hydrogel blocks, the process is completely reversible," said Dr. Sontake. "This means that individual components can also be reused."

While the structures formed so far are simple, the researchers hope to add more complexity by increasing the number of different cubes that are included in the structure and targeting different DNA strands of certain cubic faces. They also plan to increase the volume of hydrogel blocks.

"This is still fundamental research, but in the future these methods can be used in tissue engineering and regenerative medicine," said Professor Yokobayashi. "Perhaps different types of cells can be placed inside the hydrogel cubes, which can then be assembled into complex three-dimensional structures necessary for growing new tissues and organs. But regardless of the potential applications, it's amazing to be able to view chemistry as microscopically as the interaction of DNA strands with our own eyes. It's really fun science."

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