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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

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February 12, 2008

DNA Forklifts, DNA Pliers

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Posted by Derek

Manipulating nanoscale objects is a very hot research area these days, but no one’s quite sure whether it should be called physics or chemistry. The single-atom stuff (like the famous 1989 spelling of I-B-M using an early scanning tunneling microscope tip) would probably be the former, while moving whole molecules around would probably be the latter.

Now we’re to the point where you might consider it biology, since several recent papers describe ingenious uses of DNA as nanoscale pliers and Velcro. A report in Science from a group in Munich, demonstrates a nanoscale depot on a chip, formed by short DNA strands bound to its surface. Various molecules are tagged with complementary single strands of DNA. When you bring the two close enough, they hybridize, winding together spontaneously into a small double helix, which Velcros each molecule down to a defined position.

The second key to the work is that each of the molecules has a second, different DNA strand bonded to its other side. This one is complementary to a single strand attached to the tip of an atomic force microscope, so when that moves in close enough, those two hybridize as well. For the moment, the target is bound front and back.

But here's the trick: the two DNA helices are engineered so that the double helix on the bottom opens base-by-base, like a zipper, while the one on the AFM tip shears off all at once. That gives them different strengths, so when you pull up on the AFM tip, you can see the force profile of the "zipper" strand giving way as the attached molecule pulls free. Now it's dangling from the tip of the AFM, its newly freed DNA strand waving in the, uh, nano-breeze, I guess.
DNAchip.jpg
This was now moved to another portion of the chip, where more DNA strands awaited. These, like the tip strands, where also in the stonger "shear" geometry, but these were even longer, with more residues to wrap up with that free DNA strand on the molecule of interest. Lowering the two into proximity caused them to hybridize, and now pulling up on the tip caused the tip strand to unwind instead, leaving the molecule stuck on the new location on the chip. The AFM tip could then be sent back to the depot to pick up another molecule, and so on. (The illustration, courtesy of Science for nonprofit use, will give you the idea). The fluorescent molecules they used could then be imaged on the chip, confirming that they'd been arranged as expected.

The whole process took care, as you can imagine. The team kept the number of DNA strands on the tip quite low, in order to have a better idea of what was going on. Under their conditions, about one-third of the time, they picked up just one unit from the “warehouse”, and another twenty per cent of the time they got two at once. In the dropoff step at the new location, they sometimes noticed that no extra force was needed to pull the tip up, which indicated that they hadn't make a connection. In those cases, a shift of the tip assembly a few nanometers one way or another generally brought things within range for a successful transfer. It's not like you can see what's going on - light itself doesn't come small enough to let you do that in the normal sense - so you just have to feel your way along.

This is an early proof of concept, so it's not like we're going to be assembling nanomachines next week through this technique. (The DNA tags, for one thing, are rather large compared to the molecules that they're attached to). But the idea is there, and the idea works. We're starting to move single molecules around to where we want them to go, and making them stay put once they've been delivered.

Comments (2) + TrackBacks (0) | Category: Chemical News | General Scientific News


COMMENTS

1. Polymer Bound on February 12, 2008 11:10 PM writes...

Boy... I was hoping for some molecular tweezers when I couldn't get that MOM group off of my natural product at step 25 in grad school.

Too little, too late.

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2. Ruthanne Gummersheimer on March 29, 2014 12:46 PM writes...

I see they want teachers and students to join them (students get a discounted rate, woohoo! NOT!)

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