Researchers have developed a computational DNA droplet that can recognise specific combinations of chemically synthesised microRNAs (miRNAs) that serve as cancer indicators.
The droplets can serve as the computer’s molecular-input since they can provide a DNA logic computing output via physical DNA droplet phase separation. DNA droplets have been proven to execute cell-inspired applications in microcompartments.
Despite the fact that biological systems regulate their behaviour by integrating biosensing and molecular logical computation, little study has been done on coupling DNA droplets with molecular computing.
Computational DNA droplets.
The researchers started by creating Y-motifs A, B, and C, which are three different forms of Y-shaped DNA nanostructures.
These structures can create DNA droplets with the A, B, and C sequences because they have three sticky ends. Identical droplets prefer to clump together on their own, whereas dissimilar droplets require the presence of a “linker” molecule. The researchers used linker molecules labelled AB linkers and AC linkers to attach the droplets A, B, and C.
To test the “AND” procedure, the researchers used two different DNA samples in the AB droplet combination as a preliminary step in their investigation.
The value 1 indicates the presence of input, whereas the value 0 shows the absence of input in this technique. Only at condition (1,1), when both input DNAs were present, did the AB droplet mixing phase separate.
This shows that the AND operation was appropriately applied. The researchers decided that an AND input combination employing the breast cancer tumour markers miRNA-1 and miRNA-2 would yield the best outcomes based on this body of data. They could then conclude that the DNA droplet was able to recognise the miRNAs because the AND operation was successful.
The researchers went on to show that in an AB mixture containing the breast cancer biomarkers miRNA-3 and miRNA-4, they could perform simultaneous AND and NOT operations. Finally, an ABC droplet combination was produced that contained all four breast cancer biomarkers. Whether the ABC droplet separated in two or three phases was determined by the cleavage of the linker.
Using this feature of the ABC droplets, the researchers were able to show that they can simultaneously identify biomarkers for three separate diseases or a set of biomarkers linked to cancer.
According to the papers corresponding author (Prof. Masahiro Takinoue) computational DNA droplets have a lot of potential. This technology could be used for early disease detection and medicine delivery in the future if a DNA droplet capable of integrating and processing a high number of inputs and outputs can be constructed.
The new research also represents a step toward the development of artificially intelligent cells and molecular robots.
Story Source: Original press release by Tokyo Institute of Technology. Note: Content may be edited for style and length by Scible News.
References
Jing Gong, Nozomi Tsumura, Yusuke Sato, Masahiro Takinoue. Computational DNA Droplets Recognizing miRNA Sequence Inputs Based on Liquid–Liquid Phase Separation. Advanced Functional Materials, 2022; 2202322 DOI: 10.1002/adfm.202202322
