Researchers Use Engineered DNA to Develop Programmable Glue

In April, we published an update about the DNA self-assembly methods we'd reported on last year, developed by researchers at Harvard's Wyss Institute for Biologically Inspired Engineering. Then, those methods had been extended from self-assembling, two-dimensional, engineered DNA nanodevices to self-assembling, three-dimensional, engineered DNA bricks. Now, the research team has used engineered DNA to develop a programmable glue that tells which water-filled gel bricks to stick together.

These gel bricks are much larger than the nanometer-scale DNA tiles and bricks the team first developed. In those, each tile or brick had a distinct sequence of nucleotides that bound to others depending on their DNA sequence. In the new research, DNA has been used to produce glue that binds non-DNA bricks together. As before, the team is led by Peng Yin, assistant professor of systems biology at Harvard Medical School and a core faculty member at Wyss. The researchers published their work in an article in Nature Communications.

This time, the team's goal was to develop a programmable, self-assembling system for components at the mesoscale, defined as devices with edge widths of 30 microns to 1 mm. Because the researchers envisioned medical applications, they developed bricks made of biocompatible and biodegradable hydrogels containing human tissue that could self-assemble into larger, complex structures. These could aid in tissue engineering efforts focusing on regrowing biological tissue at the site of an injury. After the bricks self-assemble into the appropriate structure, they break down harmlessly as the tissues grow together.

As before, cubes only adhere to neighboring cubes with the right match of sequences. This time, self-assembly occurs after coating the hydrogel cubes with the DNA glue: snippets of engineered DNA multiplied with enzymes into long strings called "giant DNA." To make larger structures, the team coated several smaller hydrogel connector cubes with the glue and attached each one to one of the larger cubes. This effectively programs the bigger cubes to self-assemble into larger, complex shapes by bonding together with others that have connectors with appropriate sequences of matching glue.

So far, they've used this method to build shapes such as a square, a T-shaped structure, a linear chain, and a matching pair of cubes, according to a press release. The team envisions the method being used with a variety of materials to create self-assembling small-scale systems, such as surgical glue that stitches together selected tissues, reconfigurable computer chips, or lenses. Yin and Ali Khademhosseini, associate faculty member at the Wyss Institute, are the study's senior coauthors.

Other members of the team included Wyss Institute postdoctoral fellow Hao Qi, research assistant Majid Ghodousi, undergraduate researcher Casey Grun, and former postdoctoral fellow Yanan Du, now professor of biomedical engineering at Tsinghua University in Beijing, China. Also on the team was former instructor of medicine at Harvard Medical School Hojae Bae, now assistant professor of bioindustrial technologies at Konkuk University in South Korea. Research was funded by the National Institutes of Health, the Office of Naval Research, the National Science Foundation, and the Wyss Institute.

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