3D printed 'smart glue' leverages DNA assembly at the macroscale

(Nanowerk Spotlight) Designing systems that build themselves is one of the great dreams of nanotechnology researchers, and they are taking great strides towards developing such 'bottom-up' nanotechnology fabrication techniques. All biological objects are created from the bottom-up – an approach in which the order is imposed from within the object being made, so that it 'grows' according to some built-in design – but so far, this approach hasn't played as significant a role yet in technology.

Molecular assembly is quite prominently featured in popular science fiction, remember the matter compiler in Neal Stephenson's The Diamond Age or the cornucopia machine in Charles Stross' Singularity Sky ? By contrast, today's examples of bottom-up technologies are specific chemical processes that work great for a particular task, but don't easily generalize for constructing more complex structures.

Fabrication processes based on DNA might change this: DNA origami – tiny shapes and patterns self-assembled from DNA – have been heralded as a potential breakthrough for the creation of nanoscale devices.

DNA origami is a method for folding long strands of DNA into whatever very small shape or pattern you desire. Using a computer-aided design program a scientist can design the desired nanoscale shape and the computer designs a set of short DNA strands. These get mixed with long DNA strands, heated up to nearly boiling, and cooled to room temperature over the course of a couple hours. In a single drop of water one then has 100 billion copies of the desired shape, or shape with a pattern on top. The first DNA origami made were shapes like triangles and smiley faces, and patterns like maps of the western hemisphere, snowflakes, etc (read more: "DNA nanoarchitectonics").

The interesting thing about DNA origami is that it allows researchers to make such nanoscale shapes and patterns by pure self-assembly. Because random arrangements wouldn't be very useful, these patterns then need to be arranged into meaningful structures, e.g. to wire up electronic circuits (see for instance: "DNA nanotechnology in computers knocks down another roadblock") or to fabricate synthetic membrane channels.

All these ground-breaking accomplishments are strictly at the nanoscale, though, and researchers are starting to leverage the power of DNA self-assembly at a much larger scale.

New work coming out of The Ellington Lab at the University of Texas at Austin is now demonstrating that researchers indeed can build a macroscopic object held together solely by DNA interactions.

"We have developed methods to assemble DNA-functionalized microparticles into a colloidal gel, and to extrude this gel with a 3D printer at centimeter size scales," Peter Allen, formerly a researcher in the Ellington Lab and now an Assistant Professor at the University of Idaho, tells Nanowerk.

DNA crosslinked colloidal gel printed into the pyramidal shape. (Image: Allen Lab, University of Idaho)

Allen, who is first author of a paper in ACS Biomaterials Science and Engineering ("3D Printing with Nucleic Acid Adhesives") that describes the results, explains that the new process produces materials with several unique properties:

"Firstly, unlike conventional 3D printed objects, the extruded semisolids are assembled solely by DNA:DNA interactions that are strong enough to support the object at the macroscale;

Secondly, these objects have internal, microscale properties that are programmed by the nanoscale DNA interactions; by controlling the assembly of materials from the molecular to the macroscale, one of the challenges for self-assembling materials has been realized;

Thirdly, the size of these objects can be large – up to centimeters – and the cost for this material is reasonable as the bulk of its volume is an inexpensive polymer rather than expensive DNA;

And finally, this bulk material is assembled under conditions in which cells can survive and grow. This material can be 'seeded' with cells during extrusion and these cells will proliferate within the colloidal gel matrix."

He points out that the ability to apply molecular intelligence to a substrate that can make a macroscopic object is a step toward a truly rationally programmed material.

As the team describes in the paper, their colloidal gels are programmable at three distinct scales: 1) at the nanometer scale, specific DNA interactions mediate individual microparticle-to-microparticle interactions. 2) At the micrometer scale, microparticle clusters form DNA dependent substructures. This microscale topology can be further controlled by using different sizes and stoichiometries of oligonucleotide derivatized microparticles. 3) Finally, the shape of the object can be patterned at the centimeter scale by 3D printing and its material properties, such as porosity, can be altered through control over the composition of the colloidal mixtures.

Allen notes that these 3D printed, programmed, self-assembled materials present many opportunities for synthetic biology: "The final result reported in our paper was to assemble a colloidal gel from hydrogel particles. That was useful for microscopy as the hydrogel particles are very transparent. Hydrogel particles can be made with additional useful properties. I've started my new lab at the University of Idaho with this purpose: generate new types of functional particles that can be integrated into the self-assembled material."

For example, hydrogel particles can be created that release biological growth factors and that sense biological signals. The DNA-based programming of these materials can be expanded into both their assembly and their interactions with growing, developing tissue.

The key challenge is to retain and expand the 'programmability' of these DNA-bearing microparticles while simultaneously increasing the physical strength of the assembled material.

Allen cites another example: "Cells in bioprinted tissue need to have a very specific microenvironment. Generating this optimal microenvironment in a manner that scales to a usable volume is a very exciting challenge. A technology such as DNA adhesives might eventually allow this microenvironment to be self-assembled –rather than serially sculpted into some other material. The control of DNA will allow for specific structures and the cheap hydrogel will keep the overall cost low."