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DNA turbine powered by a transmembrane potential across a nanopore

nature.com

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Re: DNA turbine powered by a transmembrane potential across a nanopore

#11

Post by adr1an »

suzzer99 wrote: post #6

Here's something I've been wondering that maybe some smart hackernews-ian can explain to me. I watched a spider build a web last night. A ton of extremely complicated engineering went into it, all driven by pure instinct, presumably coded in DNA somewhere. If you gave me enough time I could lay out how a semi-conducting material turns into a T-gate transistor, which can be chained with other transistors to create AND…

You are looking to emergent properties of biological systems from a reductionist philosophical perspective. It's pretty common to have that view. I believe the nature-nurture debate of the 80s (iirc) will be of your interest.

Re: DNA turbine powered by a transmembrane potential across a nanopore

#12

Post by w10-1 »

(warning: ignorant curiosity from someone with no chemical engineering background)

This is a nice design: the chiral DNA turbine follows a leading leash into the nanopore, and the trailing cap keeps it from flowing through. The ion/electrical differential drives the turbine blades to turn (presumably the cap/leash assymmetry requires unidirectional flow).

What's unclear is how this can be converted to work in the presence of ionic flow.

It's unclear if the cap or leash could be repurposed; they're presumably spinning along with the turbine. That leaves the chiral arms, passing by the nanopore walls. I could see some charge-dependent reaction resulting from passing a charged arm-tip proximal to the nanopore-wall (enzyme), but by hypothesis we're in a charged flow so that seems like a no-go.

The converse question is whether a charged DNA arms could be induced to spin by the nanopore; that could actually drive flow (albeit likely not against any ionic or osmotic current, so it would be hard to see how it could be useful).

On the other hand, something like this might be useful not as a motor but as a discrete gating factor, e.g., to serialize flow of other molecules through a nanopore. E.g., to improve quality in the current nanopore DNA sequencing, a slow rotation time (5/s here) could enable an upstream nanopore to select one segment of DNA to be read by a downstream nanopore without the interaction of the to-be-processed segment tail with other DNA molecules near the nanopore entry. (but that might already be a solved problem for all I know.)

Re: DNA turbine powered by a transmembrane potential across a nanopore

#13

Post by captainclam »

reginaldo wrote: post #8
suzzer99 wrote: post #6

Here's something I've been wondering that maybe some smart hackernews-ian can explain to me. I watched a spider build a web last night. A ton of extremely complicated engineering went into it, all driven by pure instinct, presumably coded in DNA somewhere. If you gave me enough time I could lay out how a semi-conducting material turns into a T-gate transistor, which can be chained with other transistors to create AND…

Also interested in the answer, and I thought a bit about this and have a hypothesis that DNA does not encode everything, instead it depends on implicit assumptions about the environment. To give an example, gravity is likely not encoded in the DNA, but instead, there are many encoded behaviors that would make sense only on an environment where gravity is present. The same for the presence of predators, wind, solar ra…

Interesting! I like that thought. I enjoy thinking about how surprisingly good we are at predicting trajectories, good enough that we can throw, catch, and dodge small objects with remarkable accuracy. I wonder if our internal calculations of acceleration due to gravity is purely learned, or future space-faring infants will be surprised by how their block castles react when they knock them over.

Re: DNA turbine powered by a transmembrane potential across a nanopore

#14

Post by w10-1 »

panabee wrote: post #5
foota wrote: post #4

Earlier quoted context omitted.

See the section titled "Fluorescence microscopy data analysis". Basically, when you have a single molecule fluorescing you "just" need to do some math to figure out the center of the samples over time. See https://www.microscope.healthcare.nikon.com/products/super-r... for an overview

thanks for sharing. since you sound like an expert, do you know if this technique works for live imaging of RNA molecules or would tagging such a small molecule potentially alter biological processes and contaminate results? [edited to clarify live-imaging requirement]

FISH works for both DNA and RNA. When articles have pretty colors lighting up the inside of a cell, it's likely FISH.

First google hit is a 2020 summary of RNA-FISH, "Technical review and guide to RNA fluorescence in situ hybridization":

  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085896/

Re: DNA turbine powered by a transmembrane potential across a nanopore

#16

Post by dr_coffee »

Zee2 wrote: post #3

For some reason, what actually stands out to me in this paper is the method in which they verified the rotational motion. They used single-molecule fluorescence and optically tracked the circular trajectories that the single molecule traced out while spinning. That's the most impressive part, in my opinion... I didn't know we could even resolve fluorescing particles on that scale, much less track their trajectories o…

https://www.nature.com/articles/s41586-019-1397-7

this paper came out a few years ago using super resolution fluorescence and dna origami to track unwinding of dna by single helicase enzymes! its not an easy technique but it is doable with the right equipment (the 2014 Nobel Prize in chemistry was for super resolution microscopy)

Re: DNA turbine powered by a transmembrane potential across a nanopore

#17

Post by foota »

panabee wrote: post #5
foota wrote: post #4

Earlier quoted context omitted.

See the section titled "Fluorescence microscopy data analysis". Basically, when you have a single molecule fluorescing you "just" need to do some math to figure out the center of the samples over time. See https://www.microscope.healthcare.nikon.com/products/super-r... for an overview

thanks for sharing. since you sound like an expert, do you know if this technique works for live imaging of RNA molecules or would tagging such a small molecule potentially alter biological processes and contaminate results? [edited to clarify live-imaging requirement]

I am not exactly an expert, I just happened to do a deep dive into microscopy techniques a couple years ago :-)

The general term for these types of techniques (e.g., ones that let you image things below the "diffraction limit", which is roughly half the wavelength of light being used to image, see [1]), is super resolution microscopy[2]. There are a few other types you might find interesting.

1: https://en.wikipedia.org/wiki/Diffraction-limited_system 2: https://en.wikipedia.org/wiki/Super-resolution_microscopy

Re: DNA turbine powered by a transmembrane potential across a nanopore

#18

Post by panabee »

w10-1 wrote: post #14
panabee wrote: post #5

Earlier quoted context omitted.

thanks for sharing. since you sound like an expert, do you know if this technique works for live imaging of RNA molecules or would tagging such a small molecule potentially alter biological processes and contaminate results? [edited to clarify live-imaging requirement]

FISH works for both DNA and RNA. When articles have pretty colors lighting up the inside of a cell, it's likely FISH. First google hit is a 2020 summary of RNA-FISH, "Technical review and guide to RNA fluorescence in situ hybridization": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085896/

thanks for the link. i saw this already; it's very useful.

to clarify, the question was meant for live imaging and the risk of altering biological processes for target RNA molecules < 200 nucleotides.

Re: DNA turbine powered by a transmembrane potential across a nanopore

#19

Post by nick_rocks »

Zee2 wrote: post #3

For some reason, what actually stands out to me in this paper is the method in which they verified the rotational motion. They used single-molecule fluorescence and optically tracked the circular trajectories that the single molecule traced out while spinning. That's the most impressive part, in my opinion... I didn't know we could even resolve fluorescing particles on that scale, much less track their trajectories o…

That's absolutely fascinating! The use of single-molecule fluorescence to verify rotational motion is indeed impressive. I'm curious, how do you think this groundbreaking technique could potentially impact future research in the field?

Re: DNA turbine powered by a transmembrane potential across a nanopore

#20

Post by dekhn »

Zee2 wrote: post #3

For some reason, what actually stands out to me in this paper is the method in which they verified the rotational motion. They used single-molecule fluorescence and optically tracked the circular trajectories that the single molecule traced out while spinning. That's the most impressive part, in my opinion... I didn't know we could even resolve fluorescing particles on that scale, much less track their trajectories o…

Single molecule fluroescence has been around for a while; when I was in grad school, students in another lab were doing this. They'd label motor proteins (which use energy to move in a specific direction) to visualize them on a surface and calculate their velocity.

The particle can be much smaller than the resolution, as long as it's really bright, it will just sort of "smear out" over multiple adjacent pixels and it's possible, with some arcane trickery, to then localize to a sub-pixel.

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