The formation of aqueous droplets by liquid-liquid phase separation (or coacervation) in macromolecules is a hot topic in life science research. Among these different macromolecules that form droplets, DNA is quite interesting because it is predictable and programmable, qualities useful in nanotechnology. Recently, DNA programmability has been used to construct and regulate DNA droplets formed by coacervation of sequence-designed DNA.
A group of scientists from Tokyo University of Technology (Tokyo Tech) led by Professor Masahiro Takinoue have developed a computational DNA droplet capable of recognizing specific combinations of chemically synthesized microRNAs (miRNAs) that act as tumor biomarkers. By using these miRNAs as a molecular input, the droplets can give a logical computational output of DNA through physical phase separation of DNA droplets. Professor Takinoue explains the need for such studies: “Applications of DNA droplets have been reported in cell-inspired microcompartments. biological systems regulate their functions by combining biosensing with molecular logic computing, no literature is available on the integration of DNA droplets with molecular computing.” Their findings were published in Advanced functional materials.
Developing this DNA droplet required a series of experiments. First, they designed three types of Y-shaped DNA nanostructures called Y-patterns A, B, and C with 3 sticky ends to make DNA droplets A, B, and C. Typically, droplets similar automatically group together while to join dissimilar droplets a special “binding” molecule is needed. So, they used linker molecules to join droplet A with droplets B and C; these binding molecules have been termed AB and AC linkers, respectively.
In their first experiment, they evaluated the “AND” operation in the AB droplet mixture by introducing 2 input DNAs. In this operation, the input presence is recorded as 1 while its absence is recorded as 0. The phase separation of the AB droplet mixture occurred only at (1,1), which means that when the two Input DNAs are present, suggesting a successful application of the AND operation. As a result of this study, the scientists decided to introduce breast cancer tumor markers, miRNA-1 and miRNA-2, into the AC droplet mixture as inputs for the ET operation. The ET operation was successful, implying that the computational DNA droplet identified the miRNAs.
In subsequent experiments, the team demonstrated simultaneous AND and NOT operations in the AB mix with breast cancer biomarkers miRNA-3 and miRNA-4. Finally, they created a mixture of ABC droplets and introduced the 4 breast cancer biomarkers into this solution. The phase separation in the ABC droplet depended on the cleavage of the linker, resulting in a two-phase separation or a three-phase separation.
This property of the ABC droplet has allowed researchers to demonstrate the ability to detect a set of known cancer biomarkers or simultaneously detect markers of 3 diseases. Professor Takinoue, who is also the corresponding author, sees huge potential for computational DNA droplets. According to him, “If a DNA droplet can be developed that can integrate and process multiple inputs and outputs, we can use it in early disease detection as well as drug delivery systems. Our current study also acts as a springboard for research in the development of artificial intelligence cells and molecular robots.”
Jing Gong et al, Computational DNA Droplets Recognizing miRNA Sequence Inputs Based on Liquid-Liquid Phase Separation, Advanced functional materials (2022). DOI: 10.1002/adfm.202202322
Tokyo Institute of Technology
Quote: New Method for Early Disease Detection Using DNA Droplets (2022, June 3) Retrieved June 4, 2022 from https://phys.org/news/2022-06-method-early-disease-dna -droplets.html
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