From genes to machines

From genes to machines

(Parte 2 de 3)

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200 x 200 nm200 x 200 nm200 x 200 nm S1 (Intermdiate) S2

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Figure 3. A DNA walking device and a DNA-array-modifying device. (a) A DNA walking robot. The device consists of a ‘walker’ (brown) of two double helical domains connected by flexible linker regions. The device is held to a ‘sidewalk’ (blue) – comprising three double helical domains – by set strands (black outline). (i) Both the sidewalk and thewalkeraretailedinsingle-strandedstrandsandtheset strandsconnectthewalkerto thesidewalkattheleft twopositions.An unsetstrandremovesthesetstrand that attaches the right leg of the walker to the sidewalk (i) and (ii), and a new set strand attaches the right leg to a new position on the sidewalk (iv). The same process is repeated so that, at the end of the ‘walk’, the nanorobot has moved one step (v) and (vi). A psoralen molecule, which crosslinks the walker to the sidewalk, is used for analytical purposes (represented by a red rectangle at the bottom of each leg of the walker). (b) A 2D array capable of changing cavity dimensions. (i) A schematic strand diagram of the tiles and their incorporation into arrays. The red and purple set strands correspond to a contracted state, whereas the blue and green set strands correspond to the expanded state. (i) AFM images illustrating the control of cavity size. The ‘before’ (left), ‘transition’ (center) and ‘after’ (right) states of the array are illustrated in both directions. Part (a) reproduced, with permission, from Ref. [28]. Part (b) reproduced, with permission, from Ref. [31].

Review TRENDS in Biochemical Sciences Vol.30 No.3 March 2005 123 w.sciencedirect.com need to open it by addition of an unset strand. Nevertheless, it is does not appear impossible to use cyclic systems to control nucleic acid nanodevices in a manner similar to that used by Michael Elowitz and Stanislas Leibler to control the color of cells [50].

Concluding remarks The devices described here represent a remarkable toolbox for controlling the structural states of nucleic acid objects, and even of arrays. I suspect that the importance of the sequence selectivity (associated, so far, only with the Yurke et al. [23] control method) is the key to future progress of this field. It will come to the fore even more than it has already when numerous robust devices are incorporated into fixed positions in periodic arrays and other structures, not only as done by Yan et al. [31], but also in systems in which the devices do not modify the basic structure of the arrangement. Likewise, the extension of the Dittmer and Simmel [49] approach to complete autonomy will enable structural manifestations of logical circuits, produced perhaps by the techniques of DNA- based computation (see, for example, Ref. [12]). The toolbox will no doubt continue to grow. However, what is now required is for the DNA-nanodevices community to interact with other communities, ranging from materials science and nanoelectronics to biochemistry, genomics and molecular therapy. The value of these devices and approaches will be maximized when these diverse communities can help to establish goals for their use.

Acknowledgements

This research has been supported by grants GM-29554 from NIGMS, N00014–98–1-0093 from ONR, grants DMI-0210844, EIA-0086015, DMR-01138790, CCF-0432009 and CTS-0103002 from NSF, and an award from Nanoscience Technologies.

References

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Cleavage

Blind DissociateOpen state

Substrate (S)

Closed state Brake (B)

S2 S1 F

Removal (R) Inactive state

(a) (b) IHF

Figure 4. Advanced DNA machines. (a) A DNA-stress gauge. A DNA-distorting protein (IHF in this case) binds to the upper domain of a DNA device. The central part of this shaft connects two three-domain double helical motifs (TX motifs), and it contains the binding site for IHF. When IHF binds, it distorts the upper helix by 1608 (a smaller angle is used here for clarity). The sticky ends that hold the TX motifs together must be disrupted for the protein to bind. By titrating the strength of the sticky ends, it is possible to estimate the amount of work that the protein can derive from binding to its recognition site. The green and red circles represent donor (D) and acceptor (A) dyes that are used to monitor the state of the system by FRET. (b) An autonomous DNA machine. The machine consists of a DNAzyme that can bind and cleave a piece of RNA; when it binds, the machine is in the open state. Following cleavage of the RNA, the products are sufficiently short that they dissociate and the device closes. However, another RNA strand in the solution can bind and restore the machine to the open state. The state of the machine is monitored by FRET, using the dyes represented by black and green circles. An additional sophistication to this device is the ability to apply a brake to the system. A strand of DNA (green) can block the site, but can be removed by a complementary strand (light blue). Part (a) reproduced, with permission, from Ref. [40]. Part (b) reproduced, with permission, from Ref. [4]. q (2004) American Chemical Society (http://pubs.acs.org/journals/jacsat/).

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