 As I already hinted to you, this occurs in real proteins too. Let's start with mechanosensitive channels. So mechanosensitive channels, these are ion channels that David will likely talk a little bit more about later. They're usually surprisingly simple. These are typically just channels that are very large holes that open up to let water through in cells. And one of the reasons to let water through in cells is simply to adjust pressure. If there is too high pressure in a cell, we need to let out some water or the cell would rupture. On the other hand, the channels, these holes can't be open all the time because then the cells would be leaky. So what we'd have are channels that under normal circumstances, they sit embedded in this bilayer up here and they're closed. They are relatively thick actually, so they're not super happy in the membrane and the membrane is not super happy with them. Do you see here how the membrane has had to become slightly thicker around the channels to be able to host them? What then happens is that if I start to stretch the membrane, why would I stretch the membrane? Well, if the pressure increases in the cell, eventually this will lead to pressure building up on the membrane, right? That's going to lead to a tension in the membrane. As this tension builds up, some of these channels will now start to open. Do you see the channel on the right there opening up? So the channel itself will undergo a conformational transition, but this is really caused by when this membrane is stretched out, the lipids will have to become even thinner. Again, the volume of the lipids is roughly constant, so if I want the area to be larger when I'm adding tension, that means the thickness has to go down. Well, then the protein will have to adapt to that, otherwise it would eventually no longer be in the membrane. The way these proteins adapt to it is that when they become thinner, the actual channel opens up, as we've seen there on the light blue part. When that happens, short term, that's good. The pressure is actually relieved a bit, so that it might be sufficient for that channel to open up. Or maybe not. Maybe the pressure is starting to build up really rapidly in the cell. Now, if the pressure builds up even more rapidly, we're going to be down here, and then additional channels will open up. So now even the second channel has to open up. We didn't relieve the tension enough here. And now I have two channels where water will be able to flow out of the cell. Once that water has flown out of the cell, what happens? Well, the pressure in the cell is lower. The pressure is reduced. As the pressure is reduced inside the cell, the tension in the membrane is reduced, and then we start going back here. Maybe one channel will close. The pressure might become even lower because we're still having one channel open here, and eventually you're not going to go back here when the pressure is relieved and the channels are now closed again. This is mechanosensitive channels. You might want to have seen the abbreviation, at least it's usually called MSC, mechanosensitive channel. And then there's occasionally a small and a large one, which is called MSC, SN, MSCL. There are other proteins where this happens, not just channels, but say a protein that would like to induce curvature in the membrane. What if I insert a protein that has an almost conical shape? So here the conical shape of the, up on the upper right there, do you see what that does? That will induce a local change of the curvature in the membrane, which is of course, per se it's not good, but if we have lots of these proteins expressed, the proteins will definitely not be happy in water if they're hydrophobic. So this is going to be a balance. It's at least better for the cell to insert those proteins in the lipids. But when I do that, that will distort the lipid bilayer. If I have lots of proteins like that, I might actually start have a large global curvature of the entire bilayer. And that's what you see in some cells. For instance, certain bacteria and everything that you have a shape to the cellular bilayer by expressing specific proteins in certain parts of the cell. So we're back to this theme that lipids certainly decide what proteins will be stable in the bilayer or the membrane. But the proteins themselves, when they insert that, they in turn also influence the shape and the properties of the bilayer, either by opening it up mechanosensitive channels or by inducing curvature.