Can DNA Origami Create Programmable Nanorobots?

[Ygggdrasil]

A figure in a recent paper from Science made me smile, so I thought I'd share it with you guys. The paper describes a new way of joining nanoscale building blocks together using DNA origami. It's based on the principle that if you have two DNA double helices with a gap in between (see the blue helices in the figure below), another DNA helix that exactly matches the size of the gap (the red helix in the diagram) can snap right into create an intermolecular bond. While individually, these bonds are somewhat weak, having multiple such interactions together on a building block can create a stable, programmable way of joining blocks of DNA origami together.

In the paper, the authors build a few structures to demonstrate the versatility of the technique, but the figure that made me smile was when they built three separate pieces that would assemble into a ~ 100-nm tall "nanorobot." Just like in the cartoon Voltron, the pieces snap together to form a robot-like figure (the diagram of the structure is shown in the 3D model on the left, and electron microscopy images of the actual DNA origami structure are in the circles on the right).

The nanorobot itself does not have any applications (it doesn't actually do anything but snap togeter and open and close its arms depending on the salt concentration), but it does look neat. Probably a more useful potential application is shown in other parts of the paper where, for example, they make a box structure that can open and close (perhaps for drug delivery).

 

[Choppy]

Yes, but is it the Lion Voltron on the Vehicle Voltron?

Very cool post Ygggdrasil!

 

[Jimster41]

Okay, that is very cool in, a...sort of disturbing way. If they can make it dance, I'll take one.

Seriously though as I understand it the DNA molecule is a power house of information storage - Are there potential computing and information science applications? Blueprints to construct a whole library of organic molecules with ready made encoding, anti-entropy defense, and decoding systems...

 

[Ygggdrasil]

Seriously though as I understand it the DNA molecule is a power house of information storage - Are there potential computing and information science applications?

There have been proposals to use DNA as a sort of way to store information long term (for example, see http://newsfeed.time.com/2012/08/20/the-first-book-to-be-encoded-in-dna/). There was some interest in trying to use http://www.technologyreview.com/featuredstory/400727/dna-computing/, but I don't if anything useful ever came out of the research. There has been some work to build logical gates out of RNA in order to do very simple computations in bacteria (http://arstechnica.com/uncategorized/2008/10/rna-based-logic-gates-compute-inside-cells/).

Blueprints to construct a whole library of organic molecules with ready made encoding, anti-entropy defense, and decoding systems...

I don't really know what you mean about anti-entropy defense, but there are definitely application of DNA and biotechnology to organic synthesis. For example, David Liu's group at Harvard pioneered the use of DNA as a means to discover new chemical reactions through a process modeled after biological evolution (http://www.nature.com/nature/journal/v431/n7008/abs/nature02920.html).

 

[rollingstein]

I don't really know what you mean about anti-entropy defense, but there are definitely application of DNA and biotechnology to organic synthesis. For example, David Liu's group at Harvard pioneered the use of DNA as a means to discover new chemical reactions through a process modeled after biological evolution (http://www.nature.com/nature/journal/v431/n7008/abs/nature02920.html).

Have they discovered any novel reactions of real import by this strategy?

 

[rollingstein]

In the paper, the authors build a few structures to demonstrate the versatility of the technique, but the figure that made me smile was when they built three separate pieces that would assemble into a ~ 100-nm tall "nanorobot." Just like in the cartoon Voltron, the pieces snap together to form a robot-like figure (the diagram of the structure is shown in the 3D model on the left, and electron microscopy images of the actual DNA origami structure are in the circles on the right).

Reminds me of early STM manipulation-mode papers (circa 1990s). I think I remember IBM writing IBM on a tiny substrate with gold atoms. For a while it became a cottage industry to assemble your university's mascot etc. on a molecular scale substrate.

 

[Jimster41]

I was under the (layperson's) impression that there are worker molecules, processes, that repair existing DNA, but maybe the only anti-entropy defense is replication, with proofreading and repair. Pretty sure it does that.

It's always been my belief that the machinery we make will eventually merge with the machinery we are. But since your post I've been imagining a huge cube of DNA, just sitting in a vat if goo, doing something nature has never seen the likes of (yeah, like evolving novel proteins and whatnot) It's such a potent molecule, and process..., the doninant one on the planet really? I don't know maybe it's not good for much except seeding life.

 

[jerromyjon]

there are worker molecules, processes, that repair existing DNA

I'm pretty sure DNA is useless biologically without proteins to decode it, as well as split it apart and duplicate it. If I remember correctly there are proteins that repair damaged DNA to some extent, but beyond 106F (in human DNA?) it just falls apart. I wonder if these "contraptions" for lack of a better term, have a more temperature tolerant range of function?

 

[jerromyjon]

Telomerase reverse transcriptase is the answer to the entropy problem, perhaps?

I'mma go and make some nano-bots to take apart voltron and see how many ways they can put it back together now...

 

[Ygggdrasil]

Have they discovered any novel reactions of real import by this strategy?

I'm not sure. On David Liu's http://evolve.harvard.edu/rschdts.htm, he says "One of the discovered reactions, a carbon-carbon bond-forming macrocyclization between a simple alkyne and alkene mediated by catalytic quantities of Pd(II) in neutral water or mixed organic solvent at room temperature to form a macrocyclic trans-enone in high yield, has also been confirmed by extensive characterization in a non-DNA-templated, conventional synthesis format. Our exploration of this discovered enone-forming reaction has recently led to its successful use in an intermolecular (rather than macrocyclization) format." I don't do organic synthesis, so I'm not sure if this reaction has been widely used or not.

I was under the (layperson's) impression that there are worker molecules, processes, that repair existing DNA, but maybe the only anti-entropy defense is replication, with proofreading and repair. Pretty sure it does that.

There are proteins inside the cell that exist to repair DNA, but these obey the second law of thermodynamics and are not counteracting entropy. They do fix damage to the DNA, but the repair is coupled to the hydrolysis of ATP, which is an exergonic process that powers the repair process.

It's always been my belief that the machinery we make will eventually merge with the machinery we are. But since your post I've been imagining a huge cube of DNA, just sitting in a vat if goo, doing something nature has never seen the likes of (yeah, like evolving novel proteins and whatnot) It's such a potent molecule, and process..., the doninant one on the planet really? I don't know maybe it's not good for much except seeding life.

As @jerromyjon said, DNA won't really do any of that without the proper proteins around to decode it. In these DNA orgami applications, all it's doing is acting as a building block that can self-assemble into complex structures.

 

[jerromyjon]

At some point I foresee perhaps ultrasonic manipulation? I mean this is just the foundation, pouring all different colors of paint in a vat and you can shape rainbows so to speak, the applications are possibly limitless. If they were persuaded and/or empowered by some ultrasonic and/or electromagnetic energy... I could easily imagine building numerous, various, nanoscopic devices rather quickly. For example a 3D "forger" could create nanoparts and have some system to assemble microscopic machines, making all the pieces as they are connected in symphonies, right where they are needed by remote (short range I imagine?) control. This is all hypothetical, I don't have a very good foundation of how it could or would be implemented but it sure is fun to imagine!

I know this is crazy but plausible or not? I imagine this operation... relax and stay with us this will be quick! Heart stops. Nanobots constructing... 5, 10, 15 maybe 20 seconds... valve augmentation complete. Zap... Lub-dub.. lub-dub.. Yep, sounds good. *nanobot disintegration* See you next check-up.

 

[Mgkov18]

Are we not talking about the pokemon?

 

[RaulTheUCSCSlug]

Oh very interesting, what is the nearest application that this may have in the medical market?

 

[jerromyjon]

They already made a box that could be used to localize drug release. I have no clue what its direct applications would be.

 

[Borek]

For the record - I don't think when Jimster41 wrote about

anti-entropy defense

he meant breaking thermodynamics, more like he referred to the fact cell machinery is capable of keeping DNA unmodified (consuming energy coming from the external sources) despite natural processes degrading it. Somewhat simplified and not necessarily correct use of the term "entropy", but quite common between lay people.

 

[Jimster41]

Sorry, yes that's what I meant. Would it have been more correct to describe it as "entropy increase resistance system" or an "order maintenance system". Isn't it fair to define DNA purely in terms of entropy, since it's whole reason for being is to automatically maintain local reversibility in a non-reversible universe. The reverse action being "new cell", and even "new person". Or if that sounds too directed, the "action" of energy flow through matter that minimizes the increase of disorder?

I also could have been more clear mentioning the supporting systems that are essential to it's utility. Ribosomes, RNA, all the special "...ase" proteins, chromatin I was just thinking that nature has already built them for us also. Clearly harvesting the most sophisticated and complex machine known, is already a high priority. This post just made me realize I had never imagined that it could potentially be used in completely non-typical structures and processes to do - who knows what, in addition to curing cancer and making us all 50 feet tall.Also, they should make t-shirts and/or posters with that voltron with arms out. I would seriously buy one. Very funny and spooky, mesmerizing. An example of the great images science provides that look ambiguous or crude or weird or otherwise uninteresting, until you read the little caption... Then the stare reflex kicks in.

 

[Delta31415]

very cool post

 

[BiGyElLoWhAt]

Telomerase reverse transcriptase is the answer to the entropy problem, perhaps?

I'mma go and make some nano-bots to take apart voltron and see how many ways they can put it back together now...

^This guy -.-
I already have enough on my plate, now add yet another rabbit hole that I must see the end of.

At some point I foresee perhaps ultrasonic manipulation? I mean this is just the foundation, pouring all different colors of paint in a vat and you can shape rainbows so to speak, the applications are possibly limitless. If they were persuaded and/or empowered by some ultrasonic and/or electromagnetic energy... I could easily imagine building numerous, various, nanoscopic devices rather quickly. For example a 3D "forger" could create nanoparts and have some system to assemble microscopic machines, making all the pieces as they are connected in symphonies, right where they are needed by remote (short range I imagine?) control. This is all hypothetical, I don't have a very good foundation of how it could or would be implemented but it sure is fun to imagine!

I know this is crazy but plausible or not? I imagine this operation... relax and stay with us this will be quick! Heart stops. Nanobots constructing... 5, 10, 15 maybe 20 seconds... valve augmentation complete. Zap... Lub-dub.. lub-dub.. Yep, sounds good. *nanobot disintegration* See you next check-up.

I think plausible assuming one thing : http://www.physics.ucla.edu/research/biophysics/news/pdf/outlook.pdf
Does DNA conduct electricity? If so, this nanoscopic manipulation + conduction through these objects, perhaps using solution/air as pseudo-resistors, then you definitely have the capability for simple nanoscopic DNA-circuits or "machines". I'm not sure what you could use for a capacitors/inductors/etc... but I agree, definitely cool to think about.

Are we not talking about the pokemon?

Digimon, actually.

 

[BiGyElLoWhAt]

http://www.rsc.org/chemistryworld/News/2011/January/30011102.asp
Somewhat contradictory to the first article I posted.
"Jacqueline Barton and colleagues at the California Institute of Technology in Pasadena have shown that a 34nm strand of DNA - made up of 100 base pairs - can conduct a low current of electricity without being damaged...

"Barton's team attached a monolayer film of ordered, upright DNA strands to the surface of a gold electrode using alkanethiol tethers. They then fixed a Nile Blue redox probe - a molecule that produces a signal when a charge transfer occurs - to the other ends of the DNA strands and submerged the circuit in a phosphate buffer solution. When a low current was applied, the Nile Blue showed that the current was flowing up and down the DNA strands, not around it...

"Through cyclic voltammetry experiments Barton and her team studied the electrochemical properties of the DNA. They found that if there is a mismatch or mistake in the DNA, it will reduce the current flow by about half. 'It turns out that if you put a nick or break in the sugar phosphate backbone [of the DNA], it won't interrupt the current flow. But if you make a break in the base pairs, the current flow is 'interrupted,' she says."

A link to Jacqueline Barton's publications along with one abstract in particular that I think would be a good read, based on the abstract
http://www.its.caltech.edu/~jkbgrp/Publications.htm
http://pubs.acs.org/doi/abs/10.1021/ja107033v

Also, to put it in perspective, I want to show you what you have just done to me @jerromyjon :

 

[Jimster41]

Also, even if DNA doesn't conduct electricity, things it can make and maintain do, like neurons. Wait are neurons replenished, or not?

 

[Arsenic&Lace]

Yet another reason as to why experimental/theoretical biology (this is biophysics if I am not mistaken, to be precise) should be given more consideration by physics students!

 

[RaulTheUCSCSlug]

They already made a box that could be used to localize drug release. I have no clue what its direct applications would be.

Could you link me to the article? Does it work using the same mechanism of sodium levels? Interesting.

 

[jerromyjon]

Could you link me to the article?

Second sentence of the OP:DNA origami.
There are a few items of interest under applications, with sources.

 

[jerromyjon]

I want to show you what you have just done to me

Looks like some light reading?

 

[Ygggdrasil]

I think plausible assuming one thing : http://www.physics.ucla.edu/research/biophysics/news/pdf/outlook.pdf
Does DNA conduct electricity? If so, this nanoscopic manipulation + conduction through these objects, perhaps using solution/air as pseudo-resistors, then you definitely have the capability for simple nanoscopic DNA-circuits or "machines". I'm not sure what you could use for a capacitors/inductors/etc... but I agree, definitely cool to think about.

There are people thinking about the application of DNA origami to designing electronics at the nanoscale (mostly not taking advantage of DNA's conductivity, but that could be another interesting avenue). For example, researchers are using DNA origami to assemble gold nanoparticles for applications in biosensing, photonics, and nanoelectronics. Other research has used biological structures to assemble electronics (for example, constructing batteries from viruses), and DNA origami could, in principle, be used for similar applications (the viruses are nice because you can use their ability to evolve to improve the structures, however).

Could you link me to the article? Does it work using the same mechanism of sodium levels? Interesting.

Here's an example of a paper using DNA origami for drug delivery: http://www.nature.com/nature/journal/v459/n7243/full/nature07971.html

It uses a different principle for unlocking (not based on salt concentration), and basically acts as a sensor for certain nucleic acid sequences. This could be very useful if, for example, you have the box unlock in the presence of an mRNA that is expressed only in cancer cells.

 

[Arsenic&Lace]

Another interesting strategy being explored is using origami in tandem with SELEX like methods to "evolve" complex aptamers (e.g. a DNA nanostructure which selectively binds to a certain protein).