Biomod/2012/UTokyo/UT-Komaba/Idea
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<div id="title"><img src="http://openwetware.org/images/4/47/Biomod_2012_UTokyo_UT-Komaba_Top.png" alt="DNA tablet" width="800" height="120" onClick="this.src='http://openwetware.org/images/7/7d/BIOMOD_2012_UTokyo_UT-Komaba_title-animation.gif'"/></div>
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Idea
Mission
Now that there are many tablet computers, our goal is to create the world's smallest tablet ! We are designing and constructing a 9x12 pixels display made of DNA origami. We aim to show animation on that display, using a bistable system.
Bistable System
What is the Bistable System?
The bistable system enables us to encode two exclusive states, using a network of chemical reactions.
For example, we represent two states by materials A and B. The picture on the right side shows a reaction network implementing a bistable system using those two materials. In this network, A promotes the production of A itself and iB (i meaning inhibition), and B promotes B itself and iA. On the other hand, iA inhibits the production of A and iB inhibits production of B. There are also reactions that continuously degrade A, B, iA, and iB.
If the system is started with a larger amount of A than B, this network promotes more the production of A, which in turn will induce a decrease of B (details are shown in Simulation). Afterwards, there remains only A and vice versa if the initial conditions are opposite. Thus, thanks to the bistable system, we can make two states easily: "only A" or "only B". Any intermediate state cannot be stable and will go toward one of these two exclusive states.
Method
We design the bistable system with DNA.
- Production of A,B,iA,iB
B and iA are also produced in the same way.
- Inhibition of production of A,B
The production of B is also inhibited in the same way by iB.
- Decomposition of A,B,iA,iB (nothing means dNMPs a non-reactive monomer of DNA)
DNA tablet
What is the DNA tablet ?
The DNA tablet shows two different pictures in response to its environmental changes. We observe those pictures by AFM.
There are four kinds of pixels:
- Θ is always on (it can always be observed).
- Φ is always off (it can not be observed).
- [math]\displaystyle{ \overline{A} }[/math] can be observed when there is a lot of A in the solution.
- [math]\displaystyle{ \overline{B} }[/math] can be observed when there is a lot of B in the solution.
These pixels are made of hammerhead-like structures. They stand on DNA origami, and can be observed when they are hybridized.
Please note that both [math]\displaystyle{ \overline{A} }[/math] and [math]\displaystyle{ \overline{B} }[/math] can not be observed at the same time because the bistable system only makes the two condition; "there is only A" or "there is only B".
These four kinds of pixels enable us to switch pictures (The simulation can be seen here). Switching is very easy: you just need to switch the state of the bistable system. If you were observing the image A, then all A will disappear and B will be produced making the B image appear. Then you can switch again to come back to image A. Note that if you don't have the bistable system and you just add A (or B) strands when you want A (or B) image, after a few rounds you will end up with a concentrated mixture of A and B strands, and the images will be blurred. On the contrary the bistable keeps everything clear and reversible.
How to see it
We use AFM to see the DNA tablet. Generally an AFM detects the difference between hybridized and single-stranded ends of the staple strands on the DNA origami surface. However, even if the single strands on the DNA tablet are hybridized, they do not produce enough contrast to be seen by AFM. Hammerhead structures are sometime used as pixels with higher AFM contrast. However, they cannot be dynamically updated by hybridization-dehybridization reactions. So, we propose to use open hammerheads (pseudo-hammerheads) to produce enough contrast and still be updatable.
When the strands produced by the bistable system are hybridized, they compose a stable hammerhead and produce a good signal (figure below).
Future Works
DNA tablet with a N-stable System: More Pictures
We are sure that the size of the library can be extended by using a n-stable system. Look at the figure below.
This figure depicts a model of a tristable system. Each of A, B and C produces itself and inhibits the production of the others. Also, all of the products (A,B,C,iA,iB,iC) are degraded by the exonuclease. The degradation processes are not shown in the picture.
We can change the picture which the DNA tablet is showing since this system can realize the condition "only A" or "only B" or "only C" in the same way as the bistable system.
In a similar way, the DNA tablet can show many pictures, by using an n-stable system. In this system, each of A1, A2, A3......A(n-1) and An produces itself and inhibits the production of all the others. This system can realize all conditions "only Ak (k = 1,2,...n)".
We can represent such n-stable system by an n-sided polygon in order to make the diagram simpler (figure below). Mutual inhibition between each two of A1, A2...and An is expressed by a red line. The degradation and self-production processes are not shown.
The characteristics of the DNA-tablet with n-stable system is that we can freely switch (or preserve) the picture it is showing to any other one by changing the conditions.
Simulation of the n-stable system is here.
DNA Tablet with a N-oscillator System: Play a Movie
The DNA tablet will also be able to show a short movie by using a n-oscillator system. Look at the figure below.
The figure is a model of a trioscillator system. The difference between this figure and the one of a tristable system is that each of A, B and C produces inhibitions of production of only C, B and A (therefore, inhibitions are not mutual). In this system, the condition change makes a circle through "there is only A", "there is only B" and "there is only C", and the DNA tablet switch the pictures automatically: if A is dominant, the inhibition to C from A becomes strong, then the inhibition to B from C gets weaken, and B increases, then inhibition to A from B gets strong, and as a result B becomes dominant. Here we don't have to input some specific strands to change the pictures.
The figures below are simplified models of tristate oscillator and n-oscillator system. The difference these and those of the tristable or n-stable system is quite simple, the sides of the polygon are blue. The blue lines represent non-mutual inhibition (A inhibits all of the self-productions except B's, and B does so except C's, and....), while red ones do mutual inhibition. In this case, the state does clockwise change, like A to B to C to A, or A1 to A2 to...to An to A1.
Now we are ready to make the DNA tablet play a short movie. If we prepare slightly different images (like film frames), they change automatically and look like a movie. If you want to look at the movie in the reverse direction, you just need to change the direction of the inhibition loop.
Simulation of the n-oscillator system is here.
