6 ms·

Something I've never understood is how the nucleotides arrive to be included in the DNA strand. These animations always just show them appearing in perfect sequ

Something I've never understood is how the nucleotides arrive to be included in the DNA strand. These animations always just show them appearing in perfect sequential order when they're needed, which is of course not what happens. How are they delivered to the polymerase in the first place? How do they "know" where to be? Are there just so many of them in the cytosol that through sheer numbers, there's enough random chance they'll just shuttle into place when the polymerase needs them?

tsotnet 9y ago
As you said there are a lot of them, and they move randomly at crazy speeds (see Brownian Movement), accidentally coming together.
- fdej 9y ago
  Yes, and indeed, this is why life as we know it only works in a narrow temperature range: high enough for Brownian motion to drive reactions, low enough not to unravel the results too quickly.
dflock 9y ago
> Are there just so many of them in the cytosol that through sheer numbers, there's enough random chance they'll just shuttle into place when the polymerase needs them? Yes. Everything at that scale is very small, very close together and moving very, very fast. This kind of thing is very common at the cellular level: have a receptor/channel/process/thing that only one precise 3d molecule can fit into - and then just wait. As long as there's a process somewhere to make/acquire that molecule, then one will be along in a few nanoseconds or so, depending on the concentration. In the meantime the recipient will just wait. In this way otherwise independent processes can regulate each other, and respond in a concentration dependant way to changing conditions without any central control.
- api 9y ago
  I always thought of it as a probability field of molecules.
- amelius 9y ago
  > have a receptor/channel/process/thing that only one precise 3d molecule can fit into But what if the molecule has an unexpected "tail" attached to it? How to prevent the process from getting stuck?
  - lurker456 9y ago
    I imagine there are not many things with unexpected shapes at that level that aren't accounted for somehow. Anything that doesn't slot into it perfectly will get knocked away by collisions. Bad shapes do exist however (prions) and are a cause of diseases.
  - AstralStorm 9y ago
    Generally bulky substrates are inefficient and require additional catalysts for binding. (Typically kinases.) So something with an unexpected tail won't react. It will not occlude the receptor either because it won't bind with it reliably... These things are very, very precise.
  - deleted 9y ago
    [deleted]
kens 9y ago
I wrote a blog post a few years ago explaining how molecules get to the right place at the right time. The short answer is that cells are nothing like the nice, peaceful animations. Cells are extremely crowded and things move extremely fast. Glucose molecules, for instance, move around cells at 250 miles per hour and collides with something billions of times a second. An enzyme might collide with a reactant 500,000 times a second. And proteins can spin a million times per second. So as you suspect, by random chance molecules are in the right spot very frequently. http://www.righto.com/2011/07/cells-are-very-fast-and-crowded-places.html http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...
- modeless 9y ago
  Thank you for this. I have always figured something like this must be the case but it's never really explained very well in school.
- undershirt 9y ago
  Thank you for writing this. I used to wonder how flies have such terrific reaction times and whip around the air with insane agility. And then I wondered if we are just seeing them in fast forward, due to the relatively slow clock in our heads. I imagined it was why they had such a short lifespan of just several days. And I imagined them seeing us as glacially moving statues—"man this guy hasn't moved in years!" Reading your description of cells as moving imperceptibly fast only fills me more with this sense—that we are very slow moving giants, waiting on the billions of "years" of inner machinery time to tick us forward ever so slowly.
  - jcims 9y ago
    I've been having this same thought lately, about the scales of time that exist below/inside what we perceive. I agree that smaller/simpler brains probably run on a higher clock speed than those that are larger or more complex, and that impacts perception. But even within the fastest little minds, the rate at which chemical reactions take place or electrical signals propagate make them seem glacially slow in comparison. I was actually thinking about putting a little video together about these scales of time, with the video containing nothing more than a person's blink reaction slowed down 5,000x.
pas 9y ago
https://www.youtube.com/watch?v=VdmbpAo9JR4#t=0m51s https://www.youtube.com/watch?v=VdmbpAo9JR4#t=0m51s [warning, the view is jittery, due to being bumped around like a protein] Also interesting things, just for scale: see a bacterium and a cell nucleus: https://www.youtube.com/watch?v=mdhk_-o8_n8 https://www.youtube.com/watch?v=mdhk_-o8_n8 And an actual protein diffusion measurement from inside a nucleus (via light emitting proteins): https://www.youtube.com/watch?v=cDxUmCPxP_E https://www.youtube.com/watch?v=cDxUmCPxP_E So, we're still some time from getting a "real" picture of the nucleus. Mostly because it's so dense. (Here's a video about single particle tracking on the plasma membrane https://www.youtube.com/watch?v=dlq3kkbskaA https://www.youtube.com/watch?v=dlq3kkbskaA and the nucleus is at least a magnitude more dense/busy.) Life is very much about density gradients. Ion channels, osmotic pressure, and so on. 40% of the cytoplasm is proteins (by volume), which is remarkably high, considering a naive lattice packing is just 34% (the tetrahedral lattice with a density of).

tsotnet 9y ago

As you said there are a lot of them, and they move randomly at crazy speeds (see Brownian Movement), accidentally coming together.

fdej 9y ago
Yes, and indeed, this is why life as we know it only works in a narrow temperature range: high enough for Brownian motion to drive reactions, low enough not to unravel the results too quickly.

dflock 9y ago

> Are there just so many of them in the cytosol that through sheer numbers, there's enough random chance they'll just shuttle into place when the polymerase needs them? Yes. Everything at that scale is very small, very close together and moving very, very fast. This kind of thing is very common at the cellular level: have a receptor/channel/process/thing that only one precise 3d molecule can fit into - and then just wait. As long as there's a process somewhere to make/acquire that molecule, then one will be along in a few nanoseconds or so, depending on the concentration. In the meantime the recipient will just wait. In this way otherwise independent processes can regulate each other, and respond in a concentration dependant way to changing conditions without any central control.

api 9y ago
I always thought of it as a probability field of molecules.
amelius 9y ago
> have a receptor/channel/process/thing that only one precise 3d molecule can fit into But what if the molecule has an unexpected "tail" attached to it? How to prevent the process from getting stuck?
- lurker456 9y ago
  I imagine there are not many things with unexpected shapes at that level that aren't accounted for somehow. Anything that doesn't slot into it perfectly will get knocked away by collisions. Bad shapes do exist however (prions) and are a cause of diseases.
- AstralStorm 9y ago
  Generally bulky substrates are inefficient and require additional catalysts for binding. (Typically kinases.) So something with an unexpected tail won't react. It will not occlude the receptor either because it won't bind with it reliably... These things are very, very precise.
- deleted 9y ago
  [deleted]

kens 9y ago

I wrote a blog post a few years ago explaining how molecules get to the right place at the right time. The short answer is that cells are nothing like the nice, peaceful animations. Cells are extremely crowded and things move extremely fast. Glucose molecules, for instance, move around cells at 250 miles per hour and collides with something billions of times a second. An enzyme might collide with a reactant 500,000 times a second. And proteins can spin a million times per second. So as you suspect, by random chance molecules are in the right spot very frequently. http://www.righto.com/2011/07/cells-are-very-fast-and-crowded-places.html http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...

modeless 9y ago
Thank you for this. I have always figured something like this must be the case but it's never really explained very well in school.
undershirt 9y ago
Thank you for writing this. I used to wonder how flies have such terrific reaction times and whip around the air with insane agility. And then I wondered if we are just seeing them in fast forward, due to the relatively slow clock in our heads. I imagined it was why they had such a short lifespan of just several days. And I imagined them seeing us as glacially moving statues—"man this guy hasn't moved in years!" Reading your description of cells as moving imperceptibly fast only fills me more with this sense—that we are very slow moving giants, waiting on the billions of "years" of inner machinery time to tick us forward ever so slowly.
- jcims 9y ago
  I've been having this same thought lately, about the scales of time that exist below/inside what we perceive. I agree that smaller/simpler brains probably run on a higher clock speed than those that are larger or more complex, and that impacts perception. But even within the fastest little minds, the rate at which chemical reactions take place or electrical signals propagate make them seem glacially slow in comparison. I was actually thinking about putting a little video together about these scales of time, with the video containing nothing more than a person's blink reaction slowed down 5,000x.

pas 9y ago

https://www.youtube.com/watch?v=VdmbpAo9JR4#t=0m51s https://www.youtube.com/watch?v=VdmbpAo9JR4#t=0m51s [warning, the view is jittery, due to being bumped around like a protein] Also interesting things, just for scale: see a bacterium and a cell nucleus: https://www.youtube.com/watch?v=mdhk_-o8_n8 https://www.youtube.com/watch?v=mdhk_-o8_n8 And an actual protein diffusion measurement from inside a nucleus (via light emitting proteins): https://www.youtube.com/watch?v=cDxUmCPxP_E https://www.youtube.com/watch?v=cDxUmCPxP_E So, we're still some time from getting a "real" picture of the nucleus. Mostly because it's so dense. (Here's a video about single particle tracking on the plasma membrane https://www.youtube.com/watch?v=dlq3kkbskaA https://www.youtube.com/watch?v=dlq3kkbskaA and the nucleus is at least a magnitude more dense/busy.) Life is very much about density gradients. Ion channels, osmotic pressure, and so on. 40% of the cytoplasm is proteins (by volume), which is remarkably high, considering a naive lattice packing is just 34% (the tetrahedral lattice with a density of).