Tetris: Played in real time with microscopic optical tweezers! The video shows 42 glass microspheres (1 μm diameter) trapped by laser beams and steered by a computer.
What is an optical tweezer? Invented by Arthur Ashkin of Bell Labs in the 80’s, this is the closest we have to a tractor beam. US Secretary of Energy Steven Chu won the 1997 Nobel for its use in trapping neutral atoms. Small dielectric objects, from beads to bacteria, can be trapped by a highly focused laser beam. The force of radiation pressure is exploited to manipulate these objects. The method is sensitive enough to measure displacements of 1 angstrom: the diameter of a H atom!
Biophysicists use optical tweezers to measure movement and force generated by single molecules such as an enzyme walking along a DNA ladder or a motor like kinesin, dragging the bead along the tracks of a microtubule. (More on single molecule biophysics in subsequent posts).
I will only say that I have a hard time using real tweezers in real life. Which is very very macro compared to this.
Which means that this post must be due to absolute magic!
Optical tweezers are magic, Martha E Fay ! Imagine seeing individual steps of base addition on DNA or individual steps of a motor. Single molecule biophysics is amazing. The National Lecture at the Biophys Soc. Annual Meeting that I just attended, was given by Steven Block. I’ll post his hilarious and superb lecture when it goes online. 🙂
Optical tweezers should be used in a sci-fi thriller.
Norman Ma , or in a lab which is a sci-live thriller 🙂
Sometimes reality is more amazing than sci-fi! 🙂
A YouTube commenter’s suggestion that protozoa or bacteria might be used to replicate a game of Pac-Man seems ingenious. Just for the fun of it!
Wouldn’t this allows us to for instance re-programme or even write new programmes?
Marc Ponomareff , not quite Pac-Man, but I did watch a video of a bacterium being grabbed by the laser beam and forced to do a square dance 🙂 It was let go in the end and swam away nonchalantly. I couldn’t find the video on the web, but it is in that keynote lecture that I hope to post. At least the first half the lecture should be perfectly comprehensible to a lay audience.
I look forward to that future post; thanks for this one, too.
Thanks for being such a sport and sharing, Drew Sowersby . I will incorporate some of this in future single molecule posts, hopefully to come.
Well, Drew Sowersby , I would counter that those practical drawbacks could apply to almost any advanced lab method (anything you cannot buy a kit for!). These labs are built in basements and have to be heavily insulated. The handful of scientists who regularly use and innovate in this approach are superstars: Carlos Bustamante, Steven Block, Jim Spudich.
the optical tweezer part is actually quite easy and not magic at all. I built a rig in a grad class in 2 months and could manipulate a single polystyrene bead at a time. learned more about optics in that two months than any physics class I ever took.
Well put, Drew Sowersby . I’m less familiar with the nucleic acid work, I know the work on molecular motors better since I work on vaguely related ATPases- ion pumps.
Impressive wizardry, Justin Kiggins , for those optically challenged ones like myself 🙂
Here’s my far-more-humble optical tweezer video with not-so-humble music:
LOL, very cute Justin Kiggins ! Thanks for the share. I imagine actually placing the bead on a microtubule, waiting for a kinesin capture, then pulling at it in a “force clamp” to measure the motor steps would take a couple more months 😉
haha, yes, those are certainly the tough parts.
the “force clamp” part you actually get for free if you can measure the deviation of the bead from the center of the beam b/c they are linearly related.
Justin Kiggins : My understanding of the term comes from the analogous “voltage clamp” in electrophysiology. Doesn’t it mean that you measure the force required to keep the bead in place, against the pull of say the motor protein, that then gives you the force exerted by the motor protein? Somehow, this must be more accurate than measuring actual displacement?
So this is what happens when physics meets Amsterdam…
Yes, I think you are right, after the calibration, but if I remember right, you have a centering force gradient on your trapped bead and the maximum value for this is determined by your laser and the angle of your converging beam. The only thing you can “measure” is the displacement of the bead due to an applied force (from, say, the motor protein) which must balance with force of the laser at a given displacement from center.
Once you have that calibration down, then you can use the displacement as a feedback mechanisms to “clamp” the force during your manipulation.
I think it might also be possible to use some more clever methods like spectral scatter to judge the displacement of the bead, too? But ultimately you are using the bead displacement from the laser center as the proxy for the forces applied to it.
Drew Sowersby i’m certainly not an expert and my 2-mo prep was (obviously) without the precision needed for an experimental prep. we were just happy when we got the focal point of our camera lined up close enough to the focal point of the beam that we could see when we grabbed a bead. That took ~80 dedicated hours.
All we were looking for was a visual confirmation that the bead was being controlled by the beam.
As for actual experiments with this method, my guess is that you are looking at ~ 200 hours to build the rig (depending on how much optics background your postdocs have), then another 200 to run your primary experiment, then ~2000 to run all of your controls to make sure you’ve actually been measuring what you think you’ve been measuring 🙂
The devil is in the details, no?
Just found a really solid and detailed technical review by bustamante and others… http://alice.berkeley.edu/content/pubs/annurev.biochem.77.043007.pdf
Looks like a very clear, well-laid out review…excellent figures too. Thanks for the find, Justin Kiggins .
Change of subject, Rajini: I asked Allison for information about the role of astrocytes in neurogenesis. She referred me to you. Could you point me in the right direction?
John Condliffe , I recall three posts that I’ve made on the subject. If you enter my name and astrocytes in the search bar, they should come up (with a few repeats from reposts).
Many thanks, will do.