Scientists Developed organized structures of gel blocks from 'sticky' DNA visible to naked eye

Researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) employed minuscule DNA strands to direct the building of visible-to-the-eye gel blocks.

When mixed in a solution, the hydrogel blocks, which measure up to 2mm in length and contain DNA on their surface, self-assembled in around 10-15 minutes, according to the researchers. They published their findings in the Journal of the American Chemical Society.

Dr. Vyankat Sontakke, first author of the paper and a postdoctoral researcher in the OIST Nucleic Acid Chemistry and Engineering Unit, said, "These hydrogel blocks are, we believe, the largest things so far that have been programmed by DNA to form structured structures."

Self-assembly, in which two or more separate components interact to produce an organised structure, is prevalent in nature, with cells and DNA capable of self-assembling into extraordinarily complex microscopic structures. However, harnessing molecular interactions to control the assembly of macroscopic structures (i.e., items visible to the naked eye) is a relatively new field of research, especially with DNA.

Professor Yohei Yokobayashi, who heads the Nucleic Acid Chemistry and Engineering Unit, said, "We chose DNA because it is extremely programmable, which is due to its exquisite capacity to detect sequences."

Two single strands of DNA wrap around each other to form a double helix shape in a double-stranded DNA molecule. Bonding between bases, which fit together like a puzzle, keeps the strands together (A with T, and C with G). Scientists can use this special base pairing ability to create DNA strands that precisely match other strands and will join together.

The researchers bonded single-stranded DNA molecules to the surface of red and green-colored hydrogel blocks in one experiment. The DNA strands on the red bricks were identical to the DNA strands on the green blocks.

The matched strands of DNA bonded together when the hydrogel blocks were agitated in a solution, acting as a "glue" that held the red and green blocks together. The separated bricks self-assembled into a basic branching structure of alternating colours after ten minutes.

Importantly, the DNA strands did not interact with identical DNA strands on other blocks, preventing hydrogel blocks of the same colour from sticking together.

The scientists went on to build four pairs of matching strands to test the DNA's capacity to detect only specified sequences. They glued the single supports from the first matched pair on the red hydrogel cubes' surfaces. The green, blue, and yellow hydrogel cubes went through the same procedure.

The strands only linked with their corresponding strand when shaken together, despite the existence of many distinct DNA sequences, resulting in the previously jumbled up hydrogel blocks self-sorting into groups of the same colour.

"This demonstrates that the self-assembly process is very particular and easily programmable. We can direct the blocks to interact with each other in diverse ways by just modifying the sequence of DNA "Prof. Yokobayashi stated.

In addition to self-assembly, the researchers investigated if DNA could be used to train a structure's deconstruction. They generated two identical single-strand DNA strands, then a shorter third strand that matched part of the first strand. They used hydrogel cubes to link the initial strand and the matching shorter strand, which self-assembled when mixed in solution. The longer strand of DNA that matched the initial strand was then added to the solution, where it displaced the shorter strand over the course of an hour, causing the cubes to dismantle.

"This is incredibly interesting because it suggests that the process can be completely reversed by utilising DNA as the "glue" to hold the hydrogel blocks together," stated Dr. Sontakke. "As a result, the individual components can be reused as well."

While the structures created so far are simplistic, the researchers intend to enhance complexity by increasing the number of distinct cubes used in the construction and directing different DNA strands to certain cube faces. They also intend to make the hydrogel blocks even bigger.

"This is still fundamental research," Prof. Yokobayashi stated, "but these techniques could be employed for tissue engineering and regenerative medicine in the future." "It may be conceivable to implant various types of cells inside hydrogel cubes, which can subsequently assemble into the intricate 3-D structures required to generate new tissues and organs," says the researcher.

"However," he added. "It's wonderful to be able to see chemistry as small as interacting DNA strands with our own eyes, regardless of potential applications." It's a fascinating piece of research."

Reference:

Vyankat A. Sontakke, Yohei Yokobayashi. Programmable Macroscopic Self-Assembly of DNA-Decorated Hydrogels. Journal of the American Chemical Society, 2022; DOI: 10.1021/jacs.1c10308