8/3/2019 Thom LaBean- Hydrogels: DNA bulks up

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NEWS & VIEWS

HOM LABEAN the Departments of Computer Science and ChemistryGross Chemistry Building, Box 90345

e University, Durham North Carolina, 27708, USA.

e-mail: thomas.labean@duke.edu

DNA can now be thought of as a building materialfor macroscopic engineering projects, thanks toa study by Luo and colleagues, reported on page

of this issue, in which a self-supporting hydrogelde purely of DNA was synthesized1.Our rst understanding of DNA as a structural

terial came in the early 1950s from Franklins X-raya and the double-helix model developed by Watson

d Crick2. e sense of DNA as a physical objectderwent an important conceptual twist in the early0s when Seeman proposed the use of DNA as a

noscale building material3. DNA nanotechnologymade impressive advancements including

themunds recent use of viral genomic DNA as axible girder for the assembly of unique micro- andnoscale objects with dened shapes and surfaceterns with nanometric features4. To this backdrop

DNA as a molecular material, the paper by Luod co-workers1 adds the role of bulk macroscaleterial to DNAs repertoire, and allows us to views material as something we can hold in our hands,d which has bulk properties measurable in any

nventional materials lab.Typical double-stranded DNA is linear, and

nsequently can only form topologically linearducts. In contrast, Luo and his team use exiblenched-junction motifs to create random three-

mensional molecular networks with intriguingcroscopic properties. e creation of DNA

drogels starts with purpose-made DNA moleculesigned to associate with other complementary

ands. Molecular recognition via base pairingtates the formation of branched motifs (Fig. 1,p 1). Hydrogels form when the branched motifsociate through complementary sticky-ends with

pies of themselves (Fig. 1, step 2) and are then

bilized by the action of the enzyme ligase. Ligasecatalyst for the formation of covalent bondshe backbone of the DNA, joining two separatelecules to form a longer strand (Fig. 1, step 3).

e molecular building blocks are purposelyexibleso that the nanoscale details of the network structureare le partially to chance. is is in contrast toDNA nanotechnology constructions where a specictarget structure is sought on both the nano- and themicroscales5,6. In their synthesis, Luo and colleaguesskip the detailed nano- and microscale design infavour of engineering properties at the macroscale.eir constructs are based on three-arm (Y-type and

T-type) and four-arm (X-type) branched junctionsthat are exible and non-planar, in contrast to therigid double-crossover four-arm junctions7 (quitepopular in recent DNA nanotechnology research).

Since the 1940s DNA has been known as the genetic material connected to

heredity, and from the early 1980s it has also been considered as a potential

structural material for nanoscale construction. Now, a hydrogel made entirely of

DNA brings this molecule into the realm of bulk materials.

YDROGELS

DNA bulks up

2. Sticky-end cohesion

1. Base pairing

3. Ligation

Hydrogel

Figure 1 Short strands of complementary DNA pair up (step 1) according to their sequences of

nucleotide bases, and form flexible, branched junctions the building blocks of the DNA hydrogel.

These building blocks come together via two sequential processes: any of their arms can bind to any

other arm through base pairing (step 2) because they have so-called palindromic sticky-ends; then

enzymatic ligation (step 3) creates covalent bonds joining the backbones of abutting DNA molecules

end-to-end. This stabilizes the three-dimensional network and the bulk hydrogel that forms is strong

enough to withstand repeated cycles of drying and rehydration.

8/3/2019 Thom LaBean- Hydrogels: DNA bulks up

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EWS & VIEWS

In fact, the nanoscale details of the networkcrosslinking are unimportant, and some structuralexibility in the building units is an asset in meetingthe goal oflling space with a random network.is is not to say the hydrogels possess no short-range order on the nanoscale Luo and colleaguespresent some electron and atomic force microscopydata showing hints of periodicity consistent withthe design.

e paper also includes promising initial data onthe degradation of DNA hydrogels, incorporationof various drugs, and encapsulation of living cells.ese results point to the exciting outlook ofdeveloping DNA hydrogels for drug delivery andfor cell culture and tissue engineering purposes.is designer material could be used as an articialextracellular matrix, and as there are many enzymesavailable with which to tailor the properties of thegel and incorporate various signalling molecules, itcould provide developing cells with the proper cuesfor in vitro tissue engineering. e data so far oertantalizing hints regarding biomedical applications

including a potential cell-free protein-manufacturingtechnique for implantable and sustained drugdelivery systems.

In the on-going push to incorporate biologicalmacromolecules in engineered materials, this workshows how it is possible to do so without mimickingnature, rather through the fabrication of trulynovel materials. Although these new materials havecompositions similar to biological systems, they havebeen engineered to possess physical and mechanicalproperties never before seen in nature. Engineering ofbiological materials in non-biological ways may welllead back to biocompatible articial materials such asthe DNA hydrogels just described.

REFERENCES1. Um, S. H. et al. Nature Mater.5, 797801 (2006).

2. Watson, J. D. & Crick, F. H. C. Nature171, 737738 (1953).

3. Seeman, N. C.J.eor. Biol.99, 237247 (1982).

4. Rothemund, P. W. K. Nature440, 297302 (2006).

5. Seeman, N. C. Nature421, 427431 (2003).6. Gothelf, K. V. & LaBean, T. H. Org. Biomol. Chem.3, 40234037 (2005).

7. Li, X. J., Yang, X. P., Qi, J. & Seeman, N. C.J. Am. Chem. Soc.118,

61316140 (1996).