1. These molecules are moving around a lot. The kinetic energy of molecules at room or body temperature gives them impressive velocity relative to their scale, and they're also rotating altogether and internally.
2. Compatible molecules are like magnetic keys and locks. They attract each other and the forces align with meeting points. The same way that proteins fold spontaneously.
So the remaining part is getting concentrations appropriate for what you want to happen - and that's a matter of signaling molecules and "automatic" cell responses to changes in equilibrium. It's a really chaotic system and it's a wonder it works at all.
I imagine that's also one reason life is imprecise, i.e. no two individuals are alike even with identical genes. There's a lot of extra "entropy" introduced by that mess of a soup.
Once they are in close enough proximity to bump into each other, intermolecular forces can come into play to get the "docking process" done.
For something like transcription, once they are "docked", think of it like a molecular machine - the process by which the polymerase moves down the strands is non-random.
There are also several ways to move things around in a more coordinated fashion. Often you have gradients of ion concentration, and molecules that want to move a certain direction within that gradient. You also have microtubules and molecular machinery that moves along them to ferry things to where they need to be. You can also just ensure a high concentration of some molecule in a specific place by building it there.
1) Compartmentalizing of biological functions. Its why a cell is a fundamental unit of life, and why organelles enable more complex life. Things are physically in closer proximity and in higher concentrations where needed.
2) Multienzyme complexes. Multiple reactions in a pathway have their catalysts physically colocated to allow efficient passing of intermediate compounds from one step to the next.
https://www.tuscany-diet.net/2019/08/16/multienzyme-complexe...
3) Random chance. Stuff jiggles around and bumps into other stuff. Up until a point, higher temperature mean more bumping around meaning these reactions happen faster, and the more opportunities you can have for these components fly together in the right orientation, the more life stuff can happen more quicky. There's a reason the bread dough that apparently everyone is making now will rise faster after yeast is added if the dough is left at room temp versus allowed to do a cold rinse in the fridge. There are just less opportunities for things to fly together the right way at a lower temperature.
3a) For the ultra complex protein binding to the DNA, how those often work in reality is that they bind sort of randomly and scan along the dna for a bit until they find what they're looking or fall off. Other proteins sometimes interact with other proteins that are bound to the DNA first which act as recruiters telling the protein where to land.
This comes close -- It shows the jittery thermal motion of this tiny machinery, instead of nice smooth glides.
PS: Speed of sound is 343 m/s, diameter of a cell nucleus is ~ 0.000006m to give an idea.
Everything is being jostled around randomly. The molecules don't have brains or seeker warheads. They can't "decide" to home in on a target.
The only mechanisms for guidance are: diffusion due to concentration gradients, movement of charged molecules due to electric fields, and molecules actually grabbing other molecules.
It's all probabilities. This conformation makes it more likely that this thing will stick to this other thing. You may have heard that genes can be turned on or off. How? DNA is literally wound on molecular spools in your cell nuclei. When the DNA is loosely wound other molecules can bump into it and transcribe it -- the gene is ON. When the DNA is tightly spooled, other molecules can't get in there and the gene is OFF for transcription. There's no binary switch, just likelihoods.
Everything is probabilistic, but the probabilities have been tuned by evolution through natural selection to deliver a system that works well enough.
In the context of Covid19, I see so many people wearing PPE, but failing to act as though they understand that the actual goal is to prevent this tiny virion dust from entering your orifices. Like wearing gloves and a mask, but then picking up unclean item in store then using now unclean gloves to adjust mask and make it unclean.
People seem to think of things as having essences or talismanic effects. Like gloves give you +2 against covid and a mask gives you +5 when it's really all about preventing those virus things from bumping into your cell things.
The amount of complexity is just absolutely insane. My favourite example: DNA is read in triplets. So, for example, "CAG" adds one Glutamine to the protein it's building[1].
There are bacteria that have optimised their DNA in such a way that you can start at a one-letter offset, and it encodes a second, completely different, but still functional protein.
I found the single cell to be the most interesting subject. But of course it's a wild ride from top to bottom. The distance from brain to leg is too long, for example, to accurately control motion from "central command". That's why you have rhythm generators in your spine that are modulated from up high (and also by feedback).
Every human sensory organ activates logarithmically: Your eye works with sunlight (half a billion photons/sec) but can detect a single photon. If you manage to build a light sensor with those specs, you'll get a Nobel Prize and probably half of Apple...
When most everything is unmoving, it's "obvious"... well no, not to students, but... there's no pretense of doing anything other than stitching together an extremely selective set of "snapshots", to tell a completely bogus narrative of smooth motion.
Here it seems something like a Maya "jiggle all the things" option has been turned on. Making it sort of kind of look like you're being shown more realistic motion. But you're so not. It's the same bogus smooth narrative, now with a bit of utterly bogus jiggle. Those kinesin legs still aren't flailing around randomly. Nor only probabilistically making forward progress. And the thing it's towing still isn't randomly exploring the entire bloody space it can reach given the tether, between each and every "step". It still looks like a donkey towing a barge, rather than frog clinging to rope holding a balloon in a hurricane.
And given that the big vacuole or whatever should be flailing at the timescale defined by the kinesin feet, consider all those many much smaller proteins scattered about, just hanging out, in place, with a tiny bit of jiggle. Wow - you can't even rationalize that as being selective in "snapshots" - those proteins should just be blurs and gone.
And that's just the bogosity of motions, there's also... Oh well.
So compared with older renders, these new jiggles made it even harder to recognize that all the motion shown is bogus. And not satisfied with the old bogus motion, we've added even more. Which I suggest is dreadful from the standpoint of creating and reinforcing widespread student misconceptions. Sigh.
My favorite illustration was a video of simulated icosahedral viral capsid assembly. The triangular panels were tethered together to keep them slamming into each other. Even then, the randomness and struggle was visceral. Lots of hopeless slamming; tragic almost but failing to catch; being smashed apart again; misassembling. It was clear that without the tethers forcing proximity, there'd be no chance of successful assembly.
Nice video... it's on someone's disk somewhere, but seemingly not on the web. The usual. :/
> yeast
Nice example. For a temperature/jiggle story, I usually pair refrigerating food to slow the bacterial jiggle of life, with heating food to jiggle apart their protein origami string machines of life. With video like https://www.youtube.com/watch?v=k4qVs9cNF24 .
> Compartmentalizing
I've been told the upcoming new edition of "Physical Biology of the Cell" will have better coverage of compartmentalization. So there's at least some hope for near-term increasing emphasis in introductory content.
As a dancer, I have been fascinated by that fact. It means that dancers do not dance to the beat as they hear it - it takes too much time for the sound to be transformed by the ear/brain into an electrical pulse that reaches your leg. Instead, all dancers have a mental model of the music they dance to that is learnt by practice/repetition.
Dancing is just syncronizing that mental model to the actual rhythm that is heard. When I explained that to a bellydancer friend she finally understood the switch that she had made from being a beginning dancer to an experienced dancer who 'dances in their head'
Masks are for keeping your own particles from spreading far AND for lowering the probability of virions found in the environment from entering your respiratory system.
Masks lower the probability when all other variables are held constant. If someone thinks wearing a mask grants invincibility and in turn chooses to increase their exposure to high viral load individuals or environments, they're putting themselves at risk.
Both of you may be correct. I think the person you responded to may not have been precise in their framing.
I suspect that you had N95 masks in mind when you wrote masks, which doesn’t negate the point of the person you responded to, if they had surgical masks in mind when they wrote masks. Surgical masks are far more common than N95 masks since they are cheaper and do not provide protection against viral particles for the wearer.
Note that the 4th edition is (sortof) freely available at the NIH website. The way to navigate through that book is bizarre though, as the only way to access its content is by searching.
https://www.youtube.com/watch?v=B_zD3NxSsD8&t=3m17s
The artistic director has a ted talk where he talks about how beautiful biological processes are, and it's like no, man, you made it look that way.
If you want a really fantastic video that captures just how messy and random it is I recommend the wehi videos, like the one on apoptosis, where the proteins look way more derpy than the secret life of the cell: https://www.youtube.com/watch?v=DR80Huxp4y8 There's a couple of places where they have a hexameric protein where things magically snap into place, but I give them a pass because the kinetics on that are atrociously slow. Let's just say for the sake of a short video the cameraman happened to be at the right place at the right time.
https://www.youtube.com/watch?v=DR80Huxp4y8
here's the artistic director for the inner life of the cell (the worse one) going on and on about how "beautiful" the science of biology is:
https://www.ted.com/talks/david_bolinsky_visualizing_the_won...
http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...
But in a nutshell, the animations are heavily idealized, showing the process when it succeeds, slowing it way, way down, and totally ignoring 90% of the other nearby material so you can see what's going on. Then you remember that you have just a bajillion of cells within you, all containing this incredibly complex machinery and... it's really kindof humbling just how little we actually know about any of it. Not to discredit the biologists and scientists for whom this is their life's work; we've made incredible amounts of progress over the last century. It's just... we're peeking at molecular machinery that is so very small, and moves so quickly that it's nigh impossible to observe in realtime.
A tRNA molecule at body temperature travels at roughly 10 m/s. Assuming a point-sized tRNA and stationary ribosome of radius 125 * 10^-10 m, the ray casted by the moving tRNA will collide with the ribosome when their centers are within 125 * 10^-10 m of each other. The path of the tRNA sweeps a "collidable" circle of the radius of 125 * 10^-10 m, for a cross-sectional area of 5 * 10^-16 m^2. Multiplied by the tRNA velocity, the tRNA sweeps a volume of 5 * 10^-15 m^3 per second. Constrained inside an ordinary animal cell of volume 10^-15 m^3, the tRNA would have swept the entire volume of the cell five times over in a single second. Obviously the collision path would have significant self-overlap, but at this rate it's quite likely for the two to collide at least once any given second.
Now, consider that this analysis was only for a single ribosome/tRNA pair. A single ribosome will experience this collision rate multiplied by the total number of tRNA in the cell, on the order of thousands to millions. If a ribosome is bombarded by tens of thousands of tRNA in a single second, it's very likely one of those tRNA will (1) be charged with an amino acid, (2) be the correct tRNA for the current 3-nucleotide sequence, and (3) collide specifically with the binding site on the ribosome in the correct orientation. In actuality, a ribosome synthesizes a protein at a rate of ~10 amino acid residues per second.
Any given molecule in the cell will experience millions to billions of collisions per second. The fact that molecules move so fast relative to their size is what allows these reactions to happen on reasonable timescales.
https://smartairfilters.com/en/blog/n95-mask-surgical-preven... https://smartairfilters.com/en/blog/coronavirus-pollution-ma...
It's like how the source code to `ls` is simple because it's one of the most basic Unix programs, or something like that.
What that image drove home for me is:
1) that DNA transcription isn't something that happens rarely, or once-at-a-time. DNA is constantly being transcribed; proteins are constantly being built. The scale and rate isn't something I'd ever been taught.
2) How RNA polymerase works must be taking into account a hell of a lot of congestion. Polymerase molecules must constantly be bumping into each other.
3) How the picture would make no sense whatsoever unless you already know what the mechanism is.
I think it does make sense to start with the idealised process, as long as you follow up with messy reality.
Yeah. One might for example reduce reinforcement of the big-empty-cell misconception by briefly showing more realistically dense packing, eg [1], before fading out most of it to what can be easily rendered and seen. But that would be less "pretty". Prioritizing "pretty" over learning outcomes... is perhaps a suboptimal for education content.
> better
But still painful. Consider those quiet molecules in proteins, compared with surrounding motion. A metal nanoparticle might be that rigid, but not a protein.
One widespread issue with educational graphics, is mixing aspects done with great care for correctness, with aspects that are artistic license and utter bogosity. Where the student or viewer has no idea which aspects are which. "Just take away the learning objectives, and forget the rest" doesn't happen. More like "you are now unsalvageably soaked in a stew of misconceptions, toxic to transferable understanding and intuition - too bad, so sad".
So in what ways can samplings of a protein's configuration space be shown? And how can the surround and dynamics be shown, to avoid misrepresenting that sampling by implication?
It can be fun to picture what better might look like. After an expertise-and-resource intensive iterative process of "ok, what misconceptions will this cause? What can we show to inoculate against them? Repeat...". Perhaps implausibly intensive. I don't know of any group with that focus.
This only works if the beat you're hearing is sufficiently stable.
[1] https://cdn.rcsb.org/pdb101/molecular-machinery/ [] http://pdb101.rcsb.org/sci-art/goodsell-gallery [] http://pdb101.rcsb.org/motm/motm-by-date [] https://cdn.rcsb.org/pdb101/molecular-machinery/
To clarify: a "point particle" is an object with no internal structure, that is, it can be fully described by its coordinates wrt time (ignoring relativity for now). This is a concept, a model which explains many phenomena, a model on top of which you can build many theories. It does not, however, explain the conjunction of QM with special relativity.
I'm in Taiwan where masks are ubiquitous, and have been upset reading about the slow adoption of masks in the West because it was always from a selfish perspective ("do masks protect ME?") whereas here they're worn for a communal purpose ("how do I protect others?"). How effective they are at blocking incoming infection always seemed like a big distraction to me, since it's been clear from the start that it reduces spray from spreaders talking and coughing, which alone is enough of a reason to adopt it widely.
I know 4 billion years is a long time and the earth has a lot of matter rattling on it at any given time, but if every atom in the universe was a computer cranking out a trillion characters per second, you'd only have a 1 in a quarter quadrillion chance of making it to 'a new nation' in the first sentence of the Gettysburg address. Seeing the complexity in even the most trivial biological system just makes me scratch my head and wonder how its possible at all.
I'm not invoking God here. I just see a huge gulf in complexity that is difficult for me to traverse mentally.
No idea, sorry.
> favorite books on how things work at that scale
I've found the bionumbers database[1] very helpful. Google scholar and sci-hub for primary and secondary literature. But books... I'd welcome suggestions. I'm afraid I mostly look at related books to be inspired by things taught badly.
The bionumbers folks did a "Cell Biology by the Numbers" book... the draft is online[2].
Ha, they've done a Covid-19 by the numbers flyer[3].
If you ever encounter something nice -- paper, video, text, or whatever, or even discussion of what that might look like -- I'd love to hear of it. Sorry I can't be of more help.
[1] https://bionumbers.hms.harvard.edu/search.aspx [2] http://book.bionumbers.org/ [3] http://book.bionumbers.org/wp-content/uploads/2020/04/SARS-C...
