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October 30, 2011

First step toward a general method of creating artificial self-replicating materials of arbitrary structure and composition starting with Structural DNA seeds and tiles

New York University scientists have developed artificial structures that can self-replicate, a process that has the potential to yield new types of materials. (H/T Foresight Institute)

The discovery in Nature reports the first steps toward a general process for self-replication of a wide variety of arbitrarily designed seeds. The seeds are made from DNA tile motifs that serve as letters arranged to spell out a particular word. The replication process preserves the letter sequence and the shape of the seed and hence the information required to produce further generations.

This process holds much promise for the creation of new materials. DNA is a robust functional entity that can organize itself and other molecules into complex structures. More recently DNA has been used to organize inorganic matter, such as metallic particles, as well. The re-creation by the NYU scientists of this type of assembly in a laboratory raises the prospect for the eventual development of self-replicating materials that possess a wide range of patterns and that can perform a variety of functions. The breakthrough the NYU researchers have achieved is the replication of a system that contains complex information. Thus, the replication of this material, like that of DNA in the cell, is not limited to repeating patterns.

NYU scientists have developed artificial structures that can self-replicate, a process that has the potential to yield new types of materials. These structures consist of triple helix molecules containing three DNA double helices. Image courtesy of Nature.

Nature - Self-replication of information-bearing nanoscale patterns




DNA molecules provide what is probably the most iconic example of self-replication—the ability of a system to replicate, or make copies of, itself. In living cells the process is mediated by enzymes and occurs autonomously, with the number of replicas increasing exponentially over time without the need for external manipulation. Self-replication has also been implemented with synthetic systems, including RNA enzymes designed to undergo self-sustained exponential amplification. An exciting next step would be to use self-replication in materials fabrication, which requires robust and general systems capable of copying and amplifying functional materials or structures. Here we report a first development in this direction, using DNA tile motifs that can recognize and bind complementary tiles in a pre-programmed fashion. We first design tile motifs so they form a seven-tile seed sequence; then use the seeds to instruct the formation of a first generation of complementary seven-tile daughter sequences; and finally use the daughters to instruct the formation of seven-tile granddaughter sequences that are identical to the initial seed sequences. Considering that DNA is a functional material that can organize itself and other molecules into useful structures our findings raise the tantalizing prospect that we may one day be able to realize self-replicating materials with various patterns or useful functions.
To demonstrate this self-replication process, the NYU scientists created artificial DNA tile motifs —short, nanometer-scale arrangements of DNA. Each tile serves as a letter—A or B—that recognizes and binds to complementary letters A’ or B’. In the natural world, the DNA replication process involves complementary matches between bases—adenine (A) pairs with thymine (T) and guanine (G) pairs with cytosine (C)—to form its familiar double helix. By contrast, the NYU researchers developed an artificial tile or motif, called BTX (bent triple helix molecules containing three DNA double helices), with each BTX molecule comprised of 10 DNA strands. Unlike DNA, the BTX code is not limited to four letters—in principle, it can contain quadrillions of different letters and tiles that pair using the complementarity of four DNA single strands, or “sticky ends,” on each tile, to form a six-helix bundle.

In order to achieve self-replication of the BTX tile arrays, a seed word is needed to catalyze multiple generations of identical arrays. BTX’s seed consists of a sequence of seven tiles—a seven-letter word. To bring about the self-replication process, the seed is placed in a chemical solution, where it assembles complementary tiles to form a “daughter BTX array”—a complementary word. The daughter array is then separated from the seed by heating the solution to ~ 40 oC. The process is then repeated. The daughter array binds with its complementary tiles to form a “granddaughter array,” thus achieving self-replication of the material and of the information in the seed—and hence reproducing the sequence within the original seed word. Significantly, this process is distinct from the replication processes that occur within the cell, because no biological components, particularly enzymes, are used in its execution—even the DNA is synthetic.

“This is the first step in the process of creating artificial self-replicating materials of an arbitrary composition,” said Paul Chaikin, a professor in NYU’s Department of Physics and one of the study’s co-authors. “The next challenge is to create a process in which self-replication occurs not only for a few generations, but long enough to show exponential growth.”

“While our replication method requires multiple chemical and thermal processing cycles, we have demonstrated that it is possible to replicate not just molecules like cellular DNA or RNA, but discrete structures that could in principle assume many different shapes, have many different functional features, and be associated with many different types of chemical species,” added Nadrian Seeman, a professor in NYU’s Department of Chemistry and a co-author of the study.

13 pages of supplemental information

Non-living materials self-replicate in new process

DNA tiles
The researchers used artificial structures of DNA - so-called DNA tiles - dissolved in water to demonstrate the new process. These tiles are several tens of nanometres in size and consist of compactly folded DNA strands, from which four loose ends with a specific sequence of the bases A, C, G and T protrude. Like a barcode, these sticky ends determine the identity of a tile and ensure that tiles with complementary ends attach to each other: A always adheres to T, and C to G. When joined, the ends of the two tiles together form the characteristic double helix structure.

Sticking
The researchers arranged seven tiles with two different identities (for example indicated with the letters X and Y) to form the ‘word’ X-Y-Y-X-Y-X-Y. Subsequently, tiles with complementary sticky ends, X' and Y', spontaneously attached themselves in the right order to this initial structure (X'-Y'-Y'-X'-Y'-X'-Y'). The sticky ends only stick at a lower temperature and so the 'daughter word' was separated from the initial structure by briefly increasing the temperature. After this the researchers repeated the process with the remaining separate tiles until these formed 'granddaughters' with exactly the same XY sequence of letters .

Efficient manufacturing
This new replication process is an important step forward, as complex structures and the information enclosed in those are copied exactly. Despite using DNA, this new process is not the same as DNA copying in the cell, as no special biological machinery, such as enzymes, is used. In fact, even the DNA is synthetic, which makes the process highly robust. And best of all, the sticky DNA ends can not only be attached to DNA tiles but can also be placed on particles from a range of other materials, such as metal nanoparticles. This could make the manufacturing of new materials constructed from such building blocks far more efficient. Only one initial structure would have to be made and after that in each cycle the amount produced is doubled, which means that an exponential production rate is achieved.

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