I've been following this channel for a couple of months, since I saw your first post on Reddit, and I'm really impressed by the fact that you're still putting out these well researched videos with stunning animations! Because I think your goal is to give accurate and more detailed accounts of these molecular mechanisms than what could normally be found in a standard biochem textbook, I have several observations nitpicking things that I think could have been explained more clearly. I hope this helps someone who wants to go a bit more in depth with this fascinating topic. 0:32 If I counted correctly, the c ring drawn here seems to be made out of 12 subunits. In reality, the chloroplast ATP synthase can actually move 14 protons per rotation and it's important to note that the stoichiometry of the c ring varies from species to species (from as low as 5 to as high as 15). Generally the mitochondrial ATP synthase c ring is smaller than the chloroplast equivalent and pumps 8 protons with every full turn. 1:35 I think it's important to clarify that the job of ATP synthase is not only to synthesize ATP, the mechanism described in this video is completely reversible and the enzyme can work as a ATPase which pumps protons against their electrochemical gradient by hydrolyzing ATP. This process is especially important for some species of bacteria which in certain conditions need these proton gradients to power other mechanical processes such as movement (flagella uses a similar rotor mechanism as ATP synthase) or the transport of metabolites. However, we can also see this in the human cells, type V ATP synthases are found in the membrane of lysosomes where they acidify the interior of these organelles which are later used for digestion. 2:06 ATP to ADP is not the only energy releasing reaction used by cells, ATP can also be hydrolyzed to AMP + pyrophosphate (e.g. amino acid activation for protein synthesis, synthesis of cintrulline from argininosuccinate during the urea cycle). Moreover, other molecules similar to ATP (e.g. GTP) are sometimes used to power cellular processes. 2:35 I don't think saying that you get as many protons as possible crammed into the lumen is correct. The pH inside the lumen is around 6, so the proton concentration is "only" 10 times higher than what you see in the cytoplasm, but there is not physical reason which prohibits the pH to go ever lower than this. However, the size of the proton electrochemical gradient is capped at a specific value because at higher concentrations the protons would be leaking through the membrane at very fast rates, making the whole process too inefficient. (proton leakage means that the protons move from one side to another without passing through the ATP synthase, so their potential energy is not transformed into useful work for ATP synthesis) 2:52 As I said above, the concentration gradient is not huge, in thylakoids is at most 2 pH units wheres in mitochondria is about 0.4 pH units. In the case of mitochondria is important to say that both on the inner and outter side of the inner mitochondrial membrane there are buffer molecules which keep the pH relatively constant. If the pH were to drop inside the mitochondrion, this would lead to the denaturation of a bunch of enzyme whose catalytic activity is notoriously known for being very pH sensitive. Therefore, the energy stored in the proton gradient in this case is predominately in the form of a membrane potential (the interior of the mitochondrion is more negatively charged than the exterior), so similar to how a capacitor works. In thylakoids the opposite is true, the concentration gradient is more substantial, but the electrical component of the electrochemical gradient is reduced by the movement of Mg2+ and Cl- ions which equilibrates the charge difference between the lumen and the stroma. 5:36 It's Fo, not F0; "o" comes from oligomycin because initial experiments showed that oligomycin inhibits the function of this complex. F1 gets its name from the fact that it's water soluble and it was present in the first *f*raction isolated. 10:00 Arginine also has another important role, because of its positive charge it prevents protons from moving directly from the inner half-channel to the outer half-channel. (positive charges repel each other) 11:07 The central stalk is not entirely represented by the gamma subunit, there are also other proteins at the interface between the gamma subunit and the c ring. In mitochondria these are the sigma and the epsilon subunits; in Eubacteria there is only an epsilon subunit. As you can tell, I really love this topic and I want to end this comment with several questions about ATP synthase which still stand unresolved. I think it's important for people which have heard for the first time about ATP synthase to know that this is a field with ongoing research. Why do we see different c ring stoichiometries between species? How is the rotational movement transmitted from the c ring to the central stalk? If the central stalk rotates in steps, how is the energy stored between intermediary phases?
I am blown away by this! This is the exact kind of feedback I'm always looking for. Thank you so much for taking the time here--I cannot express enough how much I treasure this!
@@Clockworkbio I'm very glad to hear this. I'm definetely looking forward to the next video, keep up the good work! As a side note, I think the most difficult part when approaching this topic is the thermodynamics describing the proton electrochemical gradient. I think it would be cool to break down this a bit and talk about the electric and concentration component of the protonmotive force. If you plan to do a series about the mitochondrial respiratory chain I think it could fit well with that.
You seem to understand this pretty well so Ill ask you: I still dont 100% understand where the force comes from that pushes the ring. Is it the bending of the helix which, pushing against the two walls of the membrane, pushes the ring? He reiterates in the video multiple times that its "the chemical gradient pulling the ring" but that sentence doesnt really make sense to me... If its a pulling, it has to be electromagnetic force between two parts (unless its gravity, the strong, or the weak nuclear force but Im pretty sure its not :P ) so what to things are pulling on each other?
@@Lacksi12 You are correct that it is an electric force. The protons repel each other (positive charge + positive charge = repulsion), so they will spontaneously flow from the low pH side (more protons) to the higher pH side (fewer protons). Membranes are mostly non-polar, so the protons cannot spontaneously cross, which forces them to travel through ATP synthase.
I'm an aerospace engineer. I live and breath turbines. You'd be amazed by how many of my peers have never heard of ATP Synthase. These peers of mine-turbine experts in their own right-tend to have no knowledge of the most novel turbine around! I'd say they're missing out ;)
@@baloog8 if by ORC you mean organic rankine cycles, honestly no; although its not relevant to my particular specialization, I do intend to learn more about it
I'm in the same boat. I was just suggested this video. Seeing that there were no new videos after 3 years, I thought it was dead. I'm glad to hear there will be another session😊
Thank you so much for giving me and my goofy videos ~18 minutes of your life and making it all the way to that teeny little hot take. It's the only fight, comrade. We'll lose it, but we'll spend whatever slice of eternity we get beating back that current as far as we can.
Are you implying that life tends to decelerate the increase of entropy? I always assumed it accelerated it globally, even if it maintains lower entropy internally.
@@cerocero2817 Entropy supposedly always wins... But during the tussle between nuclear binding energy escaping a giant gravity fusor, and getting partially slowed by a tiny mote of molten rock-jelly... Where even more trapped binding energy and thermal energy is also trying to escape to the equilibrated suburbs of the void.... We find ourselves these little systems of what are really Gibbs Free Energy Pirates. Life. We can't exist without a pre-existing unstable system flowing down the Entropy gradient. But we hijack some of that flow, and start converting that chaos in progress into really weird islands of order. Like ATP Synthase. And even stranger, these little G pirates started RECORDING assembly instructions for these cunning little islands of order, first on linear polymers, then on dead carbohydrate corpses, then on server racks. Kinda like using Shannon Entropy in a judo flex against Thermodynamic Entropy. Big 'ole Delta S is still the heavy odds favorite in this ring, but us G Pirates are making up moves faster than ever.
This is one of the first times I have had to pause a video... think about how mind blowing is what I just watched... and then keep on going. You should have millions of subscribers...
I started watching the video thinking there is no way I am sitting through a 20 minute video on ATP synthase. I ended up watching it twice over. Genuinely thank you and very well done for putting information and presentation of this calibre for us mere mortal to see 🙏🏼
I know you're joking--but they actually give you doses of ATP for certain kinds of heart attacks and cancers! Are your biochemical processes shutting down? Screw this, science will straight up REBOOT you with an ATP injection!
As part of a cellular phosphate battery, ATP reserves AND creatine together form all your phosphate energy, after which other energy reserves need to be used to recover ATP, so yeah
I believe many people have read about ATP synthase on bio textbooks but are left wondering how protons actually turn the Fo subunit and how the turning is used to synthesize ATP. This video is exactly what I needed. Thank you so much for the great work.
I work as a TA in a university biology course, and I absolutely cannot wait to share this with my students!! This is both the most comprehensive review I've seen of ATP synthase AND the most clear, concise, and approachable explanation I've heard. I can't wait to watch more of your videos!
I lol'd at 'concise'. But thank you so much! This one was a doozy to make and I was super worried I went too in-depth on it. Excited for you to share it with your students--I really hope it helps!
Thanks so much! I hope this gives you a little inspiration to push further! The more you study--the more incredible it becomes. Just takes a little while for it to all click. It's SO VERY worth it though!
It's not a middle finger to entropy; this whole chain of energy transformation is a system that surfs the gradient of the universe's ever increasing entropy.
I came around a hypothesis that life itself might accelerate entropy in a given space. No source from my side as it got lost in the web, but an interesting thought anyways.
And once again--thanks so much for being such an important part of guiding that journey! I hope you like the video about Nitrogen Fixing and also hope I do a decent job tackling methanogenesis later this year!
Kinda weird to be reminded that an observer would think I’m being “unproductive” when I feel like learning visually is a pretty productive use of my time. I loved this vid (and series so far) other than that though!
When I took my first biochemistry class in undergrad I was blown away, I was in awe of the intelligence of the human body. Thank you for taking the time to go into such detail, this is outstanding! I didn't catch where you mentioned how many RPM this can get up to and can you comment on what determines how fast they pump? I imagine pH has to do with it and do you know how toxicity and ROS interfere with this? Can you discuss how water structure effects this, maybe you already have? Thanks again, Well Done!
8:15 - there's a simple explanation why one would call aspartic acid an aspartate: it's in ionic form, so it can be reffered to as aspartate ion (of course, it is linked with the residual protein, but nonetheless)
I've been actively looking for this for years... And it has been around for 3 years??? Oh man... You chanel is gold! I'm going to watch all I can and if one day you want to continue, I'll be glad to keep watching and liking.🤗🤗 You've made a great job, and it's a shame RUclips isn't recognising it... As I said, I wanted this but I didn't find it... I'm a biochemistry graduate now and I understand how it works, but never knew the mechanics behind. Now this hunger is satisfied, so thank you!
One of the fundamental aspects to the magic of life is the fact that it solves many problems through energy and or compartmentalization. This is a huge example of the latter. Great video. Will be waiting intently for more
The ATP synthase is powering my brain for it to understand it. I have known in crude terms how the synthase works, but it still amazes me. This and the transport enzymes walking along microtubules are among the most intriguing things in microbiology I know of.
So, I remember learning about ATP around age 13, more about it at age 15. But age 13, that was pivotal, that was where I started to understand a little more about human metabolisms, and that mine was somehow different. I now know my difference is Glycogen Storage Disorder type 5. When I was young and in shape, I noticed I had a very hard time starting. I explained it essentially as having a slow starting aerobic cycle, and not enough ATP to bring me to it. It does leave me with some curiosity though as to where my muscle energy comes from when I'm not eating ketogenically. How my body finds and moves and makes energy, and how I might improve that efficiency.
"When you're not eating ketogenic foods, your body primarily relies on glucose for energy. For someone with your condition, where glycogen storage is impaired, your body may have to turn to other sources more frequently, like breaking down fats and proteins for energy. This process, called gluconeogenesis, helps produce glucose when glycogen stores are low.To improve energy efficiency, it could be helpful to work closely with a healthcare professional who specializes in metabolic disorders. They can provide personalized guidance on nutrition, exercise, and potentially medication or supplements to support your energy needs. Additionally, focusing on a balanced diet with a mix of carbohydrates, fats, and proteins can help provide the energy your body needs while managing your condition effectively." this wut ChatGPT said
@@FroggyRibbits very accurate in fact. If I live in ketosis my body does very well because it'll live off ketones. If I am not in ketosis the next closest muscular energy source is my muscles own proteins so people with this disorder are prone to muscle wasting
Hi my name is clockwork and I am TERRIBLE at responding to comments. Thanks so much for your lovely feedback as always! I'd still trade the animations for your perspective in an INSTANT
As if the idea of a molecular turbine wasn't cool enough, I just happened to be nostalgic about the video game Syberia now, and it has a lot of clockwork machinery in it. For example, there's a fully mechanical robot (an automaton, he would correct me) who is a prominent character and one of the most endearing ones, too. Thanks to this video of yours I feel extra affinity for him, since we all share some of the same machinery :)
I developed the concept and aesthetic for this channel across ~3 years. I eventually landed on these pastels and paper cutouty style. It was only now--at this moment of reading this comment--that I realized I could have made steampunk explanations for biochemistry. I will never forgive myself for this oversight.
I love your explanation!!!! When I was a student(in 1990s) I just only heard the word ATPaseand its role, but I didn't understand the structures and exact mechanism. Now I thank to every researchers and YOU!!! I am very happy and moved to understand my body system. This machine has been developed since 3.8 billion years ago. Amazing!!!! Nature's invention is amazing!!! Thank you!!!
@@Clockworkbio I got sent here from vlogbrothers too- your videos add the perfect amount of detail to my A-Level Bio course in a way that makes everything more contextual and way easier to recall! Thank you!!
This is the best channel EVER!!! I still am wondering how someone can explain such a complicated concept so simply, go in so much detail and instigate such a curiosity and make us so emotional at the end as if it is a movie!!!MASTERPIECE
Thank you! I am a physician and am absolutely fascinated by biochemistry and physiology, but I have never heard such a helpful description of how ATP is created.
I recently switched from software engineering to paramedicine, and as someone who never took biology in HS (then spent 15 years talking about computers) videos like this are really helpful.
I like that you brought us out of the o-chem focus to make a very interesting point: "[People make dams etc. to] Harness and distribute energy with the exact same principle." I think it's also very interesting to add: with almost all of those things needing the exact same weird material to do their work: water. Liquid water flowing through the turbines of a dam. Or high temperature steam flowing through turbines in so many other kinds of power plants.
This deserves so much more attention than it has. The wuality of animation and explanation here is amazing. A wonderful refresher to the content i studied in biology and a much deeper exploration of the mechanical complexity of it all!
Thanks for taking a second at the end to reflect on the profound relationship we have to this information. You eloquently summarized why I like learning about these things. It's the closest thing I have to what others would call a religion.
Super cool video! I really wish stuff like that was available when I was at the school age, but tis' never too late to learn. Seeing mechanisms in motion makes it so,so much easier for all visual learners.
Found this video researching ATP and the Electron Transport Chain. This is the BEST explanation of the way this system works of all of the dozens of explanations I have seen. The actual MECHANICAL BENDING of the structures in the molecule spin the one part and provides MECHANICAL ROTATING Energy to create ATP!!!! My mind is blown.
As far as the re-arrangement of atomic configuration enabled by the flexibility of chemical bonds can be called mechanical in the classical sense. Otherwise (quantum-wise) everything is mechanical... Most of the proteins "just" changes it's "SHAPE" to achieve some function: in the end all of them resulting in (in)directly in the creation or destruction of some bonds (not necessarily the covalent type). It's the context which makes sense of them though...
Man this is the only video that was able to easily explain ATP synthase to me. The others just barely skimmed over these individual processes. Thank you for this. I have a lot to think about now lol
Miraculous how "Let there be Light!" was actually all of our 'birthday.' Love the idea that the plants all around us peform this miracle every single second of every single day: transforming ENERGY (sunshine) into SOLID MATTER (gluscose). And merely eating that "sunshine" (e.g. an apple) allows our bodies to perform photosynthesis in reverse: matter back into energy... Life. Even with all that MIRACULOUS stuff going on every moment of every day, your illustration of precisely how MECHANIZED it all is, is mind-blowing on a whole other level. We ARE wondrous, indeed. We ARE stardust... We ARE beautifully made.
Your not taking notice, everything is shaking and wiggling and moving, its not as stationary as the drawings show , its far more all over the place, which means the mechanics are not really life Life is the wiggling and shaking influenced by all the other wiggling and shaking , without the constant movement the machine just stops Therefore the machine is created around the FEELING and its the FEELING that gathers the machine parts together You can focus your mind on the car parts and mechanics of it all, but its not really a car until you put fire into it But we are taught to only see the parts not the fire , because we can measure the parts we cant measure the fire . its a slaver trick
PERFECT video, you have a new subscriber! My son who is studying biochemistry in high school showed me this video and introduced me to your channel. The content is classroom ready, it should be used in schools. Your channel is massively underrated. Your content deserves much more attention. Keep the great videos coming!
Loved it! My cat, too. You could double-advertise your channel as science AND cat-friendly lol He was enthralled the whole time. 'Science videos for clever cat owners'
Im going into science in first year university, and your videos are just the right amount of info so I don't feel overwhelmed. Stoked to see your 3d content soon!
I'm now finding the beauty of smaller channels You seem to process huge chunks of information in a unique way - i have the SAME CONVERSATIONS in my head Thank you for discussing these concepts with me in a way that i understand How can i donate to you while i binge watch
I'm by no means a biochemist, a medical researcher or anything in beetween. I'm a mechatronics engineer with a bit of an interest in biology, but hearing about the ATP synthase and how it not only looks like, but also behaves to a point like an electric motor just blew my mind. In my work I've heard and said many times that evolution has solved many of our engineering problems for us, but this is the most prime example I've seen to date.
VERY good video! I'm an EE with lots of science interests and this biochemistry video is captivating. In the context of the evolution of life, the vast stretch of time needed for such complex mechanisms to arise makes a great deal of sense.
WOW, YOUR METHOD IS AWESOME, I'll never forget this process, once a person fully understands a concept, it's forever. Thanks for your dedication in furthering our students in America, " Making America Great"
when i first learned about this in 9th grade it blew my mind. So much so that i still think about how my body is full of spinning machines all the time. Im glad im not the only one who finds this mechanical action fascinating.
I guess the algorithm has blessed you. While scrolling through comments I see multiple people mentioning seeing this channel for the first time, and im right there with them!
I love how it took me 8 months of pure effort to finally earn a comment from one of the coolest science communicators I know--and THEN it took me a month to respond to them. I'm just so good at this, y'all! (no seriously--thank you so much for the comment! Really excited to keep growing this library as big as you've grown yours!)
This was the best way ive ever seen this presented. Bravo sir. I hope teachers use this in biology class. And what an ending. Seriously. Thank you. I love when people share the moments where they remember their humanity, and that they are a dynamic process in the universe, just as valid and deserving as every single other process. I feel that way when I remember that every mathematical field is happening now, all around me. I'm touching them but I only know it esoteric and existentially.
The poetically beautiful ending in this video, was literally enough, for me to use my atp, and hit the subscribe and like button. And it actually made me feel better about myself. Thank you... Genuinely. Thank you.
Never seen your stuff before, Mr C Lockwork, so: I like your animation here- nicely illustrating a tricky process AND satisfying to watch endlessly. WELL DONE! Ah ATP synthesis... at school we did cover basic organic chemistry and I was caught by its glamour: the shapes and structures and logic of giant molecules: wow! Sadly when choosing exam courses for O Level I had to make a CHOICE and so dropped all 3 sciences to make room for all the subjects where I was sure of high marks. But always stayed a science freak in my bones!
Excellent Explanation of the Mitochondria. The best I have ever seen about this subject. Kudos to you. Excellent explanation beautifully animated. Thank you.
Incredible video info (from my view- I didn't study bio) and the last part was very good and something that a ton of people need to hear, and listen to. Me too probably.
This is one of the coolest things ever and fantastic explanation! Never knew this is how it all worked. Also since I was a kid, with very bad ADHD/HFA, I was always fascinated by almost anything that spins. Fans, propellors, roof vent turbines, you name it I liked it. The fact that the F0 Complex is like a little merry-go-round makes me 5 again. Me simple, spinny thing go brrrrrrrrrrrrrrrrrrrrrrrrrr
very good work by you. You are going pretty in depth about this topic but still process it in a way that makes it pretty easy to understand. keep up the good work.
I'm blown away by your excellent video on this nano motor that turns at 7800rpm. This frequency is what got my attention while scanning youtube yesterday. Go search for an online audio frequency generator, put on some noise cancelling headphones, tune to 7800hz and you will hear the same hiss that I, and many others affected by tinnitus, 'hear' 24 hours a day. I my case, it is constant in both frequency and amplitude. About ten years ago my awareness of this 'hiss' became severe enough for me to seek medical help but to no avail. I learned that it was not an externally generated effect and was caused by neuro transmission in the brain, but why that frequency? I'm satisfied with this correlation now and would be interested in your take on it.
Instant subscription. What an incredibly video that really does a good job of centering the awe and reverence of the natural world that I believe should be foundational to a love of science!
I always used to hate molecular/cellular biology, just because they would always stop at the part where they simply said it was a rotor turning the synthase. Once I got to a class where they actually begun explaining how these charges lead to conformational changes in proteins it all just became so incredibly fascinating. Something like learning how protein coats help bend and bud vesicles just floored me. So incredibly cool.
After the last comment I decided to sit, drink, eat a snack, make sure all my engines firing on all cylinders and start working on my thesis. Subscribed.
I know you made this video several years ago, but I thought I'd let you know that folks out there still finding it and enjoying it. This is one of the best vpapers on ATP synthesis that I've ever seen. Fantastic work... Liked and subed. LoL
Really its extremely meta to use the power of ATP Synthase to learn about and imagine how ATP Synthase. It's really amazing to think that after 4 billion years evolution finally produced a being capable of being awed by its own beauty and I feel extremely blessed to have this ability and to live at a time where I can learn about all of these wonders. It might have taken 13,7 billion years but now there's finally a creature in this universe capable of understanding its beauty. That's the beauty of being human, that's the beauty of science.
I didn't realize ATP Synthase was a motor. I remember trying to learn how cilia and flagella work without muscles and seeing the insanely complex motor proteins driving them. I understood absolutely nothing, but I was blown away by the complexity, and how similar it is to a real motor, with a stator, rotor, etc. I WILL understand how they work one day. Even if it takes me 10 years. (I'm self taught for 25+ years).
I watched this video and was blown away then realized that the subscribe button never loaded so I reloaded and slapped the button as soon as it appeared in case it was going to run away when the page finished loading.
Just did a project on this protein. It works much more efficiently than the most powerful vehicle engines ever engineered by many folds. It’s mind boggling to learn this.
I've been following this channel for a couple of months, since I saw your first post on Reddit, and I'm really impressed by the fact that you're still putting out these well researched videos with stunning animations! Because I think your goal is to give accurate and more detailed accounts of these molecular mechanisms than what could normally be found in a standard biochem textbook, I have several observations nitpicking things that I think could have been explained more clearly. I hope this helps someone who wants to go a bit more in depth with this fascinating topic.
0:32 If I counted correctly, the c ring drawn here seems to be made out of 12 subunits. In reality, the chloroplast ATP synthase can actually move 14 protons per rotation and it's important to note that the stoichiometry of the c ring varies from species to species (from as low as 5 to as high as 15). Generally the mitochondrial ATP synthase c ring is smaller than the chloroplast equivalent and pumps 8 protons with every full turn.
1:35 I think it's important to clarify that the job of ATP synthase is not only to synthesize ATP, the mechanism described in this video is completely reversible and the enzyme can work as a ATPase which pumps protons against their electrochemical gradient by hydrolyzing ATP. This process is especially important for some species of bacteria which in certain conditions need these proton gradients to power other mechanical processes such as movement (flagella uses a similar rotor mechanism as ATP synthase) or the transport of metabolites. However, we can also see this in the human cells, type V ATP synthases are found in the membrane of lysosomes where they acidify the interior of these organelles which are later used for digestion.
2:06 ATP to ADP is not the only energy releasing reaction used by cells, ATP can also be hydrolyzed to AMP + pyrophosphate (e.g. amino acid activation for protein synthesis, synthesis of cintrulline from argininosuccinate during the urea cycle). Moreover, other molecules similar to ATP (e.g. GTP) are sometimes used to power cellular processes.
2:35 I don't think saying that you get as many protons as possible crammed into the lumen is correct. The pH inside the lumen is around 6, so the proton concentration is "only" 10 times higher than what you see in the cytoplasm, but there is not physical reason which prohibits the pH to go ever lower than this. However, the size of the proton electrochemical gradient is capped at a specific value because at higher concentrations the protons would be leaking through the membrane at very fast rates, making the whole process too inefficient. (proton leakage means that the protons move from one side to another without passing through the ATP synthase, so their potential energy is not transformed into useful work for ATP synthesis)
2:52 As I said above, the concentration gradient is not huge, in thylakoids is at most 2 pH units wheres in mitochondria is about 0.4 pH units. In the case of mitochondria is important to say that both on the inner and outter side of the inner mitochondrial membrane there are buffer molecules which keep the pH relatively constant. If the pH were to drop inside the mitochondrion, this would lead to the denaturation of a bunch of enzyme whose catalytic activity is notoriously known for being very pH sensitive. Therefore, the energy stored in the proton gradient in this case is predominately in the form of a membrane potential (the interior of the mitochondrion is more negatively charged than the exterior), so similar to how a capacitor works. In thylakoids the opposite is true, the concentration gradient is more substantial, but the electrical component of the electrochemical gradient is reduced by the movement of Mg2+ and Cl- ions which equilibrates the charge difference between the lumen and the stroma.
5:36 It's Fo, not F0; "o" comes from oligomycin because initial experiments showed that oligomycin inhibits the function of this complex. F1 gets its name from the fact that it's water soluble and it was present in the first *f*raction isolated.
10:00 Arginine also has another important role, because of its positive charge it prevents protons from moving directly from the inner half-channel to the outer half-channel. (positive charges repel each other)
11:07 The central stalk is not entirely represented by the gamma subunit, there are also other proteins at the interface between the gamma subunit and the c ring. In mitochondria these are the sigma and the epsilon subunits; in Eubacteria there is only an epsilon subunit.
As you can tell, I really love this topic and I want to end this comment with several questions about ATP synthase which still stand unresolved. I think it's important for people which have heard for the first time about ATP synthase to know that this is a field with ongoing research.
Why do we see different c ring stoichiometries between species? How is the rotational movement transmitted from the c ring to the central stalk? If the central stalk rotates in steps, how is the energy stored between intermediary phases?
I am blown away by this! This is the exact kind of feedback I'm always looking for. Thank you so much for taking the time here--I cannot express enough how much I treasure this!
@@Clockworkbio I'm very glad to hear this. I'm definetely looking forward to the next video, keep up the good work!
As a side note, I think the most difficult part when approaching this topic is the thermodynamics describing the proton electrochemical gradient. I think it would be cool to break down this a bit and talk about the electric and concentration component of the protonmotive force. If you plan to do a series about the mitochondrial respiratory chain I think it could fit well with that.
You seem to understand this pretty well so Ill ask you: I still dont 100% understand where the force comes from that pushes the ring. Is it the bending of the helix which, pushing against the two walls of the membrane, pushes the ring?
He reiterates in the video multiple times that its "the chemical gradient pulling the ring" but that sentence doesnt really make sense to me...
If its a pulling, it has to be electromagnetic force between two parts (unless its gravity, the strong, or the weak nuclear force but Im pretty sure its not :P ) so what to things are pulling on each other?
@@Lacksi12 You are correct that it is an electric force. The protons repel each other (positive charge + positive charge = repulsion), so they will spontaneously flow from the low pH side (more protons) to the higher pH side (fewer protons). Membranes are mostly non-polar, so the protons cannot spontaneously cross, which forces them to travel through ATP synthase.
It works in reverse gear too! Amazing.
I'm an aerospace engineer. I live and breath turbines. You'd be amazed by how many of my peers have never heard of ATP Synthase. These peers of mine-turbine experts in their own right-tend to have no knowledge of the most novel turbine around! I'd say they're missing out ;)
Gives whole new meaning to turbomolecular pump..😂
Do you know ORCs pretty well?
@@baloog8 if by ORC you mean organic rankine cycles, honestly no; although its not relevant to my particular specialization, I do intend to learn more about it
@@reidmock2165 cool, you may want to look up OTEC as that is a great intro into ORC turbines.
Car loan doesn't mean shit. Get it?
How the hell am I discovering this only 3 years after the upload? First time I understood how ATP works as an energy source!
Honestly--it's the best time to meet the channel. Everyone else had to wait years for season 2--you're only going to have to wait about a month!
I'm in the same boat. I was just suggested this video. Seeing that there were no new videos after 3 years, I thought it was dead.
I'm glad to hear there will be another session😊
The algorithm works in mysterious ways. Just got pushed to me as well.
@@Clockworkbio plz bruh don't die, we really love your content. If possible, plz make a video about CRISPR CAS9 gene editing used in gene therapy
@@Clockworkbio OHHHHH BOY OH BOY OH BOY 😃
"A cool little middle finger raised up to entropy and chemical equilibrium."
Ah, I see you fight the good fight.
Thank you so much for giving me and my goofy videos ~18 minutes of your life and making it all the way to that teeny little hot take.
It's the only fight, comrade. We'll lose it, but we'll spend whatever slice of eternity we get beating back that current as far as we can.
If you're not a Writer,
You should start.
fuck entropy and chemical equilibrium all my homies hate entropy and chemical equilibrium
Are you implying that life tends to decelerate the increase of entropy? I always assumed it accelerated it globally, even if it maintains lower entropy internally.
@@cerocero2817 Entropy supposedly always wins...
But during the tussle between nuclear binding energy escaping a giant gravity fusor, and getting partially slowed by a tiny mote of molten rock-jelly...
Where even more trapped binding energy and thermal energy is also trying to escape to the equilibrated suburbs of the void....
We find ourselves these little systems of what are really Gibbs Free Energy Pirates.
Life.
We can't exist without a pre-existing unstable system flowing down the Entropy gradient. But we hijack some of that flow, and start converting that chaos in progress into really weird islands of order.
Like ATP Synthase.
And even stranger, these little G pirates started RECORDING assembly instructions for these cunning little islands of order, first on linear polymers, then on dead carbohydrate corpses, then on server racks.
Kinda like using Shannon Entropy in a judo flex against Thermodynamic Entropy.
Big 'ole Delta S is still the heavy odds favorite in this ring, but us G Pirates are making up moves faster than ever.
“A cool little middle finger raised up to entropy and chemical equilibrium”
Give this man a Nobel 😂
1:51 "it takes a lot of energy to be alive" - I feel that bro
This is one of the first times I have had to pause a video... think about how mind blowing is what I just watched... and then keep on going.
You should have millions of subscribers...
I started watching the video thinking there is no way I am sitting through a 20 minute video on ATP synthase. I ended up watching it twice over. Genuinely thank you and very well done for putting information and presentation of this calibre for us mere mortal to see 🙏🏼
This is why i add ATP to my morning coffee.
I know you're joking--but they actually give you doses of ATP for certain kinds of heart attacks and cancers! Are your biochemical processes shutting down? Screw this, science will straight up REBOOT you with an ATP injection!
So creatine?
(you cannot eat atp its not bioavailable regardless of what suppliment companies say)
@@ToniMorton well creatine isn't really ATP, I think it just helps ADP recover back into ATP as far as I understand
As part of a cellular phosphate battery, ATP reserves AND creatine together form all your phosphate energy, after which other energy reserves need to be used to recover ATP, so yeah
I believe many people have read about ATP synthase on bio textbooks but are left wondering how protons actually turn the Fo subunit and how the turning is used to synthesize ATP. This video is exactly what I needed.
Thank you so much for the great work.
Lovely synopsis of entire ATP synthase process. Thanks R_M
It's bloody criminal how few views this video has. You deserve more. Your product is energizing and fundamental.
I work as a TA in a university biology course, and I absolutely cannot wait to share this with my students!! This is both the most comprehensive review I've seen of ATP synthase AND the most clear, concise, and approachable explanation I've heard. I can't wait to watch more of your videos!
I lol'd at 'concise'. But thank you so much! This one was a doozy to make and I was super worried I went too in-depth on it. Excited for you to share it with your students--I really hope it helps!
I had biology in my freshman year but due to online classes just read enough to pass. This is just incredible illustration! Got yourself a new sub.
Thanks so much! I hope this gives you a little inspiration to push further! The more you study--the more incredible it becomes. Just takes a little while for it to all click. It's SO VERY worth it though!
This was honestly the most helpful explanation of ATP synthase that I could find on the Internet. Thanks a lot!
It's not a middle finger to entropy; this whole chain of energy transformation is a system that surfs the gradient of the universe's ever increasing entropy.
Right, it’s like a fridge - locally decreasing entropy in exchange for a global increase in
I came around a hypothesis that life itself might accelerate entropy in a given space. No source from my side as it got lost in the web, but an interesting thought anyways.
@@VigiHunter It was told by Schrodinger himself
@@kartikpoojari22 thank you!
Tuis is what happens when you put energy in a box for an infinite amount of time
As an industrial automation guy, I see a lot of similarity between the processes I deal with and biological processes like this.
you guys did a great job with those astromech units
You should look up amino acid production and the citric acid cycle.
"This is only the beginning of our biochemical journey together." Damn. Almost got chills. Can't wait to see what else you've got in store for us!
And once again--thanks so much for being such an important part of guiding that journey! I hope you like the video about Nitrogen Fixing and also hope I do a decent job tackling methanogenesis later this year!
@@Clockworkbioare you planning any more videos?
Kinda weird to be reminded that an observer would think I’m being “unproductive” when I feel like learning visually is a pretty productive use of my time. I loved this vid (and series so far) other than that though!
When I took my first biochemistry class in undergrad I was blown away, I was in awe of the intelligence of the human body. Thank you for taking the time to go into such detail, this is outstanding! I didn't catch where you mentioned how many RPM this can get up to and can you comment on what determines how fast they pump? I imagine pH has to do with it and do you know how toxicity and ROS interfere with this? Can you discuss how water structure effects this, maybe you already have? Thanks again, Well Done!
8:15 - there's a simple explanation why one would call aspartic acid an aspartate: it's in ionic form, so it can be reffered to as aspartate ion (of course, it is linked with the residual protein, but nonetheless)
Thats so interesting! Also, does it have absolutely any correlation with aspartame?
Thanks 😊
Thanks John green for suggesting this channel . That guy keeps helping my brain . Animations are slick !!!!
I've been actively looking for this for years... And it has been around for 3 years??? Oh man... You chanel is gold! I'm going to watch all I can and if one day you want to continue, I'll be glad to keep watching and liking.🤗🤗
You've made a great job, and it's a shame RUclips isn't recognising it... As I said, I wanted this but I didn't find it... I'm a biochemistry graduate now and I understand how it works, but never knew the mechanics behind. Now this hunger is satisfied, so thank you!
One of the fundamental aspects to the magic of life is the fact that it solves many problems through energy and or compartmentalization. This is a huge example of the latter. Great video. Will be waiting intently for more
Thanks so much! Got a fresh one coming for you in the next 24 hours!
The ATP synthase is powering my brain for it to understand it. I have known in crude terms how the synthase works, but it still amazes me. This and the transport enzymes walking along microtubules are among the most intriguing things in microbiology I know of.
So, I remember learning about ATP around age 13, more about it at age 15.
But age 13, that was pivotal, that was where I started to understand a little more about human metabolisms, and that mine was somehow different.
I now know my difference is Glycogen Storage Disorder type 5.
When I was young and in shape, I noticed I had a very hard time starting. I explained it essentially as having a slow starting aerobic cycle, and not enough ATP to bring me to it.
It does leave me with some curiosity though as to where my muscle energy comes from when I'm not eating ketogenically. How my body finds and moves and makes energy, and how I might improve that efficiency.
"When you're not eating ketogenic foods, your body primarily relies on glucose for energy. For someone with your condition, where glycogen storage is impaired, your body may have to turn to other sources more frequently, like breaking down fats and proteins for energy. This process, called gluconeogenesis, helps produce glucose when glycogen stores are low.To improve energy efficiency, it could be helpful to work closely with a healthcare professional who specializes in metabolic disorders. They can provide personalized guidance on nutrition, exercise, and potentially medication or supplements to support your energy needs. Additionally, focusing on a balanced diet with a mix of carbohydrates, fats, and proteins can help provide the energy your body needs while managing your condition effectively."
this wut ChatGPT said
@@FroggyRibbits very accurate in fact. If I live in ketosis my body does very well because it'll live off ketones. If I am not in ketosis the next closest muscular energy source is my muscles own proteins so people with this disorder are prone to muscle wasting
Okay, seriously, your animations are soo good and I love your presentation style in this one!
Hi my name is clockwork and I am TERRIBLE at responding to comments. Thanks so much for your lovely feedback as always! I'd still trade the animations for your perspective in an INSTANT
As if the idea of a molecular turbine wasn't cool enough, I just happened to be nostalgic about the video game Syberia now, and it has a lot of clockwork machinery in it. For example, there's a fully mechanical robot (an automaton, he would correct me) who is a prominent character and one of the most endearing ones, too. Thanks to this video of yours I feel extra affinity for him, since we all share some of the same machinery :)
I developed the concept and aesthetic for this channel across ~3 years. I eventually landed on these pastels and paper cutouty style.
It was only now--at this moment of reading this comment--that I realized I could have made steampunk explanations for biochemistry.
I will never forgive myself for this oversight.
@@Clockworkbio This style is great and original - semi-paper, semi-vector. I particularly like the electrons
@@Clockworkbiowell seems like it's time to start working at it again as youtube seemingly is promoting your videos, and fair enough
I love your explanation!!!!
When I was a student(in 1990s) I just only heard the word ATPaseand its role, but I didn't understand the structures and exact mechanism.
Now I thank to every researchers and YOU!!!
I am very happy and moved to understand my body system.
This machine has been developed since 3.8 billion years ago.
Amazing!!!!
Nature's invention is amazing!!!
Thank you!!!
blogbrothers sent me and I'm so happy they did --this is great!
I'm so glad you're here--and I really hope I keep making videos that are a good use of your time! Thanks so much!
@@Clockworkbio I got sent here from vlogbrothers too- your videos add the perfect amount of detail to my A-Level Bio course in a way that makes everything more contextual and way easier to recall! Thank you!!
This is the best channel EVER!!! I still am wondering how someone can explain such a complicated concept so simply, go in so much detail and instigate such a curiosity and make us so emotional at the end as if it is a movie!!!MASTERPIECE
Thank you! I am a physician and am absolutely fascinated by biochemistry and physiology, but I have never heard such a helpful description of how ATP is created.
I recently switched from software engineering to paramedicine, and as someone who never took biology in HS (then spent 15 years talking about computers) videos like this are really helpful.
I like that you brought us out of the o-chem focus to make a very interesting point: "[People make dams etc. to] Harness and distribute energy with the exact same principle." I think it's also very interesting to add: with almost all of those things needing the exact same weird material to do their work: water. Liquid water flowing through the turbines of a dam. Or high temperature steam flowing through turbines in so many other kinds of power plants.
This deserves so much more attention than it has. The wuality of animation and explanation here is amazing. A wonderful refresher to the content i studied in biology and a much deeper exploration of the mechanical complexity of it all!
Amazing thanks for this video. I quit biochemistry 20 years ago. It was difficult for me. Now I’m realising after visualising all. It is interesting.
Thanks for taking a second at the end to reflect on the profound relationship we have to this information. You eloquently summarized why I like learning about these things. It's the closest thing I have to what others would call a religion.
Super cool video! I really wish stuff like that was available when I was at the school age, but tis' never too late to learn. Seeing mechanisms in motion makes it so,so much easier for all visual learners.
Found this video researching ATP and the Electron Transport Chain. This is the BEST explanation of the way this system works of all of the dozens of explanations I have seen. The actual MECHANICAL BENDING of the structures in the molecule spin the one part and provides MECHANICAL ROTATING Energy to create ATP!!!! My mind is blown.
As far as the re-arrangement of atomic configuration enabled by the flexibility of chemical bonds can be called mechanical in the classical sense. Otherwise (quantum-wise) everything is mechanical...
Most of the proteins "just" changes it's "SHAPE" to achieve some function: in the end all of them resulting in (in)directly in the creation or destruction of some bonds (not necessarily the covalent type). It's the context which makes sense of them though...
Excellent work. I hope bio students appreciate your work because I sure wish this was available when I was a student.
Man this is the only video that was able to easily explain ATP synthase to me. The others just barely skimmed over these individual processes. Thank you for this. I have a lot to think about now lol
Miraculous how "Let there be Light!" was actually all of our 'birthday.' Love the idea that the plants all around us peform this miracle every single second of every single day: transforming ENERGY (sunshine) into SOLID MATTER (gluscose). And merely eating that "sunshine" (e.g. an apple) allows our bodies to perform photosynthesis in reverse: matter back into energy... Life.
Even with all that MIRACULOUS stuff going on every moment of every day, your illustration of precisely how MECHANIZED it all is, is mind-blowing on a whole other level.
We ARE wondrous, indeed. We ARE stardust... We ARE beautifully made.
Your not taking notice, everything is shaking and wiggling and moving, its not as stationary as the drawings show , its far more all over the place,
which means the mechanics are not really life
Life is the wiggling and shaking influenced by all the other wiggling and shaking , without the constant movement the machine just stops
Therefore the machine is created around the FEELING and its the FEELING that gathers the machine parts together
You can focus your mind on the car parts and mechanics of it all, but its not really a car until you put fire into it
But we are taught to only see the parts not the fire , because we can measure the parts we cant measure the fire . its a slaver trick
PERFECT video, you have a new subscriber! My son who is studying biochemistry in high school showed me this video and introduced me to your channel. The content is classroom ready, it should be used in schools. Your channel is massively underrated. Your content deserves much more attention. Keep the great videos coming!
I wanted to take a moment to express my admiration for the exceptional work you did in this video. Your passion for the subject is truly inspiring.
This is so in depth and illustrative, I love it!
And if I had the talent to sound design as well as you do--I would be LITERALLY UNSTOPPABLE. Thanks so much for taking the time to watch this!
Loved it! My cat, too. You could double-advertise your channel as science AND cat-friendly lol He was enthralled the whole time. 'Science videos for clever cat owners'
Yo I genuinely thought my cat was just weird for like, ALWAYS watching while I'm animating these! I need more data. We gotta find more cats!
Im going into science in first year university, and your videos are just the right amount of info so I don't feel overwhelmed. Stoked to see your 3d content soon!
I'm now finding the beauty of smaller channels
You seem to process huge chunks of information in a unique way - i have the SAME CONVERSATIONS in my head
Thank you for discussing these concepts with me in a way that i understand
How can i donate to you while i binge watch
I'm by no means a biochemist, a medical researcher or anything in beetween. I'm a mechatronics engineer with a bit of an interest in biology, but hearing about the ATP synthase and how it not only looks like, but also behaves to a point like an electric motor just blew my mind. In my work I've heard and said many times that evolution has solved many of our engineering problems for us, but this is the most prime example I've seen to date.
VERY good video! I'm an EE with lots of science interests and this biochemistry video is captivating. In the context of the evolution of life, the vast stretch of time needed for such complex mechanisms to arise makes a great deal of sense.
WOW, YOUR METHOD IS AWESOME, I'll never forget this process, once a person fully understands a concept, it's forever. Thanks for your dedication in furthering our students in America, " Making America Great"
Great video. Thanks for clarifying that we aren’t just speaking metaphorically, it’s powered and actually spins
when i first learned about this in 9th grade it blew my mind. So much so that i still think about how my body is full of spinning machines all the time. Im glad im not the only one who finds this mechanical action fascinating.
I guess the algorithm has blessed you. While scrolling through comments I see multiple people mentioning seeing this channel for the first time, and im right there with them!
These animations are looking so good! Awesome library you're building
I love how it took me 8 months of pure effort to finally earn a comment from one of the coolest science communicators I know--and THEN it took me a month to respond to them. I'm just so good at this, y'all!
(no seriously--thank you so much for the comment! Really excited to keep growing this library as big as you've grown yours!)
Your video is so great, that no one disliked it! I didn't know I want to understand biochemistry.
This was unexpectedly incredible. The ending swept me off my feet. Thank you so much!
This was the best way ive ever seen this presented. Bravo sir. I hope teachers use this in biology class.
And what an ending. Seriously. Thank you. I love when people share the moments where they remember their humanity, and that they are a dynamic process in the universe, just as valid and deserving as every single other process.
I feel that way when I remember that every mathematical field is happening now, all around me. I'm touching them but I only know it esoteric and existentially.
came to study for a biochem test, left with a tear. thank you
Love everything what you do! Thank you for being there!
Very excited to see this type of content coming with this style of animation. It's fantastic
Took me a good long while to develop--so I'm really excited that it works for this genre. Thanks so much for your feedback!
The poetically beautiful ending in this video, was literally enough, for me to use my atp, and hit the subscribe and like button. And it actually made me feel better about myself. Thank you... Genuinely. Thank you.
This takes me back to college! Also the ending was so inspirational. I love learning about the small details of chemistry. Water is underrated!
Not me crying. Thank you for these videos.
One of the best videos on this. I would definitely take a longer version of this with much more molecular detail because how could you not want it?
Thanks for answering the proton question, I've been wondering 😂
Graduating in 1970 in Honours Biochem, I see the progress in knowledge and the stunning advance in graphics that amazes.
Never seen your stuff before, Mr C Lockwork, so: I like your animation here- nicely illustrating a tricky process AND satisfying to watch endlessly. WELL DONE! Ah ATP synthesis... at school we did cover basic organic chemistry and I was caught by its glamour: the shapes and structures and logic of giant molecules: wow! Sadly when choosing exam courses for O Level I had to make a CHOICE and so dropped all 3 sciences to make room for all the subjects where I was sure of high marks. But always stayed a science freak in my bones!
God damn, that final bit about not feeling like you need to prove yourself hit me completely by surprise. I needed that. Thanks
Excellent Explanation of the Mitochondria.
The best I have ever seen about this subject.
Kudos to you.
Excellent explanation beautifully animated.
Thank you.
I'm really enjoying these videos. Keep up the great work!
Trying really hard--thank you so much! Hope I can keep up this level of quality.
Thank you for help us understand the enormous complexity that is needed for life to exist.
That was a really impactful message at the end
Your video was excellent, I can NOT wait to see what else you have. Immediately shared with my nerdy group chat, immediately subscribed.
Incredible video info (from my view- I didn't study bio) and the last part was very good and something that a ton of people need to hear, and listen to. Me too probably.
This is one of the coolest things ever and fantastic explanation! Never knew this is how it all worked. Also since I was a kid, with very bad ADHD/HFA, I was always fascinated by almost anything that spins. Fans, propellors, roof vent turbines, you name it I liked it. The fact that the F0 Complex is like a little merry-go-round makes me 5 again. Me simple, spinny thing go brrrrrrrrrrrrrrrrrrrrrrrrrr
This is my all time favorite biological processes. I loved learning about this in anatomy and physiology
very good work by you. You are going pretty in depth about this topic but still process it in a way that makes it pretty easy to understand. keep up the good work.
you have such a soothing voice and talk about really interesting things
I'm blown away by your excellent video on this nano motor that turns at 7800rpm. This frequency is what got my attention while scanning youtube yesterday. Go search for an online audio frequency generator, put on some noise cancelling headphones, tune to 7800hz and you will hear the same hiss that I, and many others affected by tinnitus, 'hear' 24 hours a day. I my case, it is constant in both frequency and amplitude. About ten years ago my awareness of this 'hiss' became severe enough for me to seek medical help but to no avail. I learned that it was not an externally generated effect and was caused by neuro transmission in the brain, but why that frequency? I'm satisfied with this correlation now and would be interested in your take on it.
Replying to my error of a factor of 60 on the previous post. I'll have to keep searching...
I was not expecting such nice reassurances at the end of what i thought was a good background noise video :,)
Instant subscription. What an incredibly video that really does a good job of centering the awe and reverence of the natural world that I believe should be foundational to a love of science!
I always used to hate molecular/cellular biology, just because they would always stop at the part where they simply said it was a rotor turning the synthase. Once I got to a class where they actually begun explaining how these charges lead to conformational changes in proteins it all just became so incredibly fascinating. Something like learning how protein coats help bend and bud vesicles just floored me. So incredibly cool.
As a physicist it took everything I had to resist getting triggered by the magnets/electrical charges conflation in the section about water.
I have no words for how amazing this is
Yea but the words you wrote here were pretty good tho.
After the last comment I decided to sit, drink, eat a snack, make sure all my engines firing on all cylinders and start working on my thesis. Subscribed.
I know you made this video several years ago, but I thought I'd let you know that folks out there still finding it and enjoying it. This is one of the best vpapers on ATP synthesis that I've ever seen. Fantastic work... Liked and subed. LoL
Season 2 drops in a little over a month! Real happy folks are finding me before I kick it back into high gear!
Really its extremely meta to use the power of ATP Synthase to learn about and imagine how ATP Synthase. It's really amazing to think that after 4 billion years evolution finally produced a being capable of being awed by its own beauty and I feel extremely blessed to have this ability and to live at a time where I can learn about all of these wonders. It might have taken 13,7 billion years but now there's finally a creature in this universe capable of understanding its beauty. That's the beauty of being human, that's the beauty of science.
3 years later and YouTubr finally recommends me this gem. Love it❤
Perfect timing too-season 2 is just over a month away!
The amazing thing is that this was figured out !
Clockwork I liked the connection to the watermill and the turbine.
Wow. I just found your channel from this video and I'm very impressed with the quality of this. Thank you ❤
I didn't realize ATP Synthase was a motor. I remember trying to learn how cilia and flagella work without muscles and seeing the insanely complex motor proteins driving them. I understood absolutely nothing, but I was blown away by the complexity, and how similar it is to a real motor, with a stator, rotor, etc. I WILL understand how they work one day. Even if it takes me 10 years. (I'm self taught for 25+ years).
The end of this video was pure poetry!
I am always blown away by biochemistry but this time was specially mindbending
I watched this video and was blown away then realized that the subscribe button never loaded so I reloaded and slapped the button as soon as it appeared in case it was going to run away when the page finished loading.
Just did a project on this protein. It works much more efficiently than the most powerful vehicle engines ever engineered by many folds. It’s mind boggling to learn this.
This content deserves more views.
It's amazing that we exist at all. All of these complex cellular mechanisms are absolutely amazing.
Watching this while working out... Raw
the ending was really beautiful, thank you!