From genes to machines: DNA nanomechanical devices

Abstract

The structural properties that enable DNA to serve so effectively as genetic material can also be used for other purposes. The complementarity that leads to the pairing of the strands of the DNA double helix can be exploited to assemble more complex motifs, based on branched structures. These structures have been used as the basis of larger 2D and 3D constructions. In addition, they have been used to make nanomechanical devices. These devices range from DNA-based shape-shifting structures to gears and walkers, a DNA-stress gauge and even a translation device. The devices are activated by mechanisms as diverse as small molecules, proteins and, most intriguingly, other molecules of DNA.

Figure 1. Early DNA Nanomechanical Devices

(a) A Device Based on DNA Supercoiling. The system consists of a small DNA circle that contains a permanent cruciform. The four nucleotide pairs at the base of the cruciform are capable of branch migration, because they are the same in both arms of the extruded cruciform (left). When the circle is relaxed by the addition of an intercalator, the mobile nucleotide pairs move to the circle. (b) A Device Based on the B-Z Transition of DNA. Two DX molecules (red and blue) are connected by a shaft that contains 20 nucleotide pairs (yellow) that are capable of undergoing the B-->Z transition. In the B-state, both domains are on the same side of the shaft (top), but when Co(NH₃) ³⁺₆ is added to the solution, the system switches to the Z-state, and the domains are on opposite sides of the shaft. The red and green circles represent a pair of dyes for a FRET measurement.

Figure 2. The PX-JX₂ Device and its Applications

(a) The Machine Cycle of the PX-JX₂ Device. The PX molecule (left) contains green set strands that are removed (process I) by unset strands that are biotinylated (black dots). The resulting naked frame (top) can be bound by pink set strands (process II) to put the device in the JX₂ state. Note that the bottoms have been rotated by a half-turn between the two states. Processes III and IV so that the same operations (with appropriate strands) can be used to restore the system to the PX state. (b) A System to Demonstrate the Motion of the PX-JX₂ Device. DNA trapezoids are connected by the device. When the system is in the PX state, all trapezoids point in the same direction, but they point in opposite directions in the JX₂ state. (c) Atomic Force Microscopy Images of the Molecules in (b). The PX and the JX₂ strings show the images expected from the schematics in (b). (d) A Translation Device Based on the PX-JX₂ Device. A DNA diamond and two double diamonds are connected by two different PX-JX₂ devices; the one on the left is in the PX state, and the one on the right is in the JX₂ state. This arrangement establishes an order of Arabic numerals along the top of the device that will bind a particular pair of DX molecules; in this case, the molecules labeled DX2 and DX5 are selected for ligation. There is no transcriptional relationship between the set strands in the devices and the sequences in the product.

Figure 3. A DNA Walking Device and a DNA Array-Modifying Device

(a) A DNA Walking Robot. The device consists of brown double helices connected by a flexible linker. It is held to a blue sidewalk by set strands [1]. The rightmost set strand is removed [2] and [3]), and a new set strand attaches the right leg to a new position on the sidewalk. [4]. The same process is repeated in [5] and [6] so that at the end of the walk, the nanorobot has moved one step. The red mark at the bottom of each leg of the walker represents a psoralen molecule that crosslinks the walker to the sidewalk for analytical purposes. (b) A Two-Dimensional Array Capable of Changing Cavity Dimensions. The upper panel shows a schematic strand diagram of the tiles and their incorporation into arrays. The red and purple set strands correspond to a contracted state, while the blue and green set strands correspond to the expanded state. The lower panel shows AFM images that illustrate control of cavity size. The ‘before’ (left), ‘transition’ (center) and ‘after’ (right) states of the array are illustrated in both directions. Reproduced with permission.

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 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. The TX motifs are also held together by sticky ends that must be disrupted for the protein to bind. By titrating the strength of the sticky ends, it is possible to estimate that amount of work that the protein can derive from binding to its recognition site. The green and red circles represent a pair of dyes 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 (upper left). Following cleavage (upper right), the products dissociate from the device (middle). However, another RNA strand can bind and restore the machine to the open state. The state of the machine is monitored by FRET, using the dyes represented by filled circles. An additional sophistication to this device is the ability to apply a brake to the system. This is shown as the green strand, made of DNA, which can block the site, but which can be removed by a complementary strand (light blue). Reproduced with permission.