 This is a so-called amphiphatic molecule, very typical of lipids, all of them are amphiphatic. And amphiphatic, if you remember when we talked about hydrophobicity, that means that we have one part of the molecule that's fat-loved, like oil. And then we have one part here that is water-loving or fairly soluble, the head group. There are many names here. These molecules are actually synthesized in your body from a glycerol. And then we have two fatty acid chains here that bind. So occasionally we talk about these, the fatty acid chains, the glycerol, and the head group. There are even more fun parts here. Do you see that there is a blue atom up there? So this is an NH3 group, same type of group as we have on the lysine side chain. So we actually have a full plus one unit charged on this lipid here. Do you see that there is a yellow atom there? There you probably see it. That's a phosphate group. You've seen phosphates before in say ADP and ATP. And the phosphate, well, just as a phosphate ion, all the oxygen surrounding this means that we have a net minus one charge here. So you have a plus one charge here and a minus one charge in the head group. Where have we seen this before? That's right, in the amino acids. So this entire head group here, it's zwitterionic, very common for lipids. There are lipids that have positively charged head groups. There are also some lipids that have negatively charged head groups. In fact, the negatively charged ones are slightly more common on the surface of our cells. But I would say that the most common lipids are zwitterionic. So they're exceptionally polar. They will love, they have to be sold in water. You can't put this in a fat or oil face. And then we have this transition group, the linker here, the glycerol, that then binds to these long purely uncharged hydrophobic tails. These hydrophobic tails, they will hate to be water. So there is no way the molecule would ever behave like this if I just threw it in a solvent. The only reason why it's behaving like this is that I'm hiding all its neighbors around it. So this is again from a molecular simulation of a lipid bilayer. Of course, people couldn't do that in the 1950s. So I bet that you've all seen these idealized movies of what a lipid bilayer looks like. I'm going to show you one of them in a few seconds. But in the meantime, I will show you what else we can do with molecular simulations today. So when I was a PhD student, some 20 years ago, slightly more even, computers were finally getting fast enough that we could simulate lipid bilayers. And in fact, I wrote the large parts of my thesis on them. And that made us ask the question that couldn't we really simulate the process? What happens if you start to throw these in water? And do we, in fact, get bilayers, which we did together with Sivir Jan Marenk? So let's just take a bunch of them and throw them in a small periodic box. And this is again a bit of rehash of the molecular simulation lecture. So do you see that the light blue lines here, that's a periodic box. But just to stress that this is a continuum, I drawn periodic copies on all sides of the box so that effectively we have an infinite path of lipids with the tails in purple. You have the charged head groups or the sweater ionic head groups in this case, in orange or yellow. And then we are drawing the waters in light blue as very thin lines, otherwise you wouldn't see the lipids. And then we start the clock. And already within like a nanosecond or so, it goes exceptionally fast. You get a hydrophobic collapse of the tail parts. So you see here that the tails are then forming some sort of blobs. And then you have a periodic image and that's why it looks like you're having multiple blobs. But it's almost just one blob in this cell. You're going to lose sight of me for a second because I'm going to need to put another image here. Another few nanoseconds later, you almost formed a periodic structure here. Well, it is a periodic structure, but it's still fully mixed up with water and everything. So there's water holes going straight through this nascent bilayer, as we call it. And the head groups are pointing everywhere. There are some head groups on the inside of the bilayer. There are some lipid chains exposed on the outside and everything. What then happens after say, 20 pickers and nanoseconds or so, I think it's this. Now, all the head groups are now facing the outside because it was so expensive to put the head groups inside lipid bilayer. And you see now that you have a pure water face out here and a pure water face on the other side. And they are in fact in contact with each other since it's periodic. There is still some sort of hole through this bilayer, roughly here, you see. And you might not see it ideally here, but there are even some head groups pointing to the inside of that hole. That actually makes sense because if we had a hole with water through it, that water would be exposed to the hydrocarbon interior, the hydrophobic parts. And that would be very expensive. So the lipids that would normally face the water, well, they would look like this. In this case, some of them are still facing the inside of this pore. So on one side, they look like that. These are my hydrophilic parts. And then they're facing the pore and then on the outside. And that's a somewhat stable part because to break this, we now need to break that water pore. And this turns out to be stable for maybe 15 nanoseconds or so. And then eventually, we're getting to a transition state where this water pore is collapsing. And a little bit after that, we have a beautiful continuous bilayer formed. This was just an example. And I'm not sure whether we got the energetics and timescales absolutely correct. But the whole idea is that we it's very obvious that these bilayers will form rapidly. There will be some sort of free energy during the formation of this process. And again, the reason for this is to rehash what you've learned. So initially, we start out at the relatively high free energy, right? And then we're getting a drop in free energy due to the hydrophobic collapse. We want that. And then it keeps going down. But to actually, and then we're in a fairly stable situation here where we have this water, we might even go down a little bit more. We have this water pore formed and the lipids are not really exposing anything to anything hydrophobic to the water. But we still have the water pore and eventually there's going to be some sort of free energy barrier. We have to get over what we closed that water pore and then eventually you get down to a really stable state where we formed the bilayer. Again, this is drawn purely qualitatively. But just from looking at a process like that, you should be able to draw a curve like this. You should also be able to guess what happens here that the reason for this free energy barrier is mostly entropy, right? That we need to break that water pore that's going to lead to exposed hydrophobic compounds, hydrophobic compounds exposed to the water, hydrogen bond reformation and everything. It's going to be some searching. It will take a while to get over it. But eventually this is going to be a more advantageous state. Let's look at what that lifted bilayer looks like in the interior.