1 00:00:00,980 --> 00:00:06,260 So for example, 820. 2 00:00:11,770 --> 00:00:20,379 All right. So, um. Yeah. My name is Alex. Uh, I have just joined very recently the, um, uh, the theory, uh, physics here in Oxford. 3 00:00:20,380 --> 00:00:22,720 And I'm really enjoying this a lot. 4 00:00:22,720 --> 00:00:31,270 And I want to tell you a little bit about, um, uh, the research, uh, that I have been doing that I am doing, um, and also introduce this, uh, 5 00:00:31,270 --> 00:00:39,159 this, this presentation a little bit with some, some general thoughts, um, on, on what is going on in the field and making some arguments. 6 00:00:39,160 --> 00:00:46,600 Why? Um, I also think that physics, um, has maybe some interesting things to say about, um, processes, uh, like this. 7 00:00:47,110 --> 00:00:55,719 So what you see here is, you know, probably really one of the, of the atomistic unit of, of developing an organism. 8 00:00:55,720 --> 00:01:00,340 What you have to do, it's a single round cell that we begin with. 9 00:01:00,340 --> 00:01:03,909 We are looking at this, a cross section, um, and of course, 10 00:01:03,910 --> 00:01:09,340 biologically what is happening in the cell division is that the genome that you see 11 00:01:09,340 --> 00:01:14,350 also slightly in some different contrast here in the middle through this process, 12 00:01:14,710 --> 00:01:20,800 it's distributed to the two daughter cells. Uh, that's uh, that, this, this uh, movie ends up with. 13 00:01:21,400 --> 00:01:25,480 And so this is clearly the biological one of the many biological functions of this process. 14 00:01:25,870 --> 00:01:33,670 Um, but I hope you can also agree with me that it is also a very fascinating physical process, if we think about this as a materialist, 15 00:01:34,060 --> 00:01:41,020 seems to be a material that is able autonomously to change its shape in a very coordinated way, 16 00:01:41,590 --> 00:01:45,819 and our experience with changing the shape of a material. 17 00:01:45,820 --> 00:01:47,850 What, maybe something like this, right. 18 00:01:47,890 --> 00:01:54,580 If we if we take a rubber ball and we I asked you to change its shape, what you naturally would probably do is to, to squeeze it. 19 00:01:54,670 --> 00:02:00,700 Um, and that's what do the job. Um, but what that means is you have to apply a force. 20 00:02:00,700 --> 00:02:06,070 Um, and obviously, uh, there's no one, uh, squeezing the cell that you just saw in this movie. 21 00:02:06,340 --> 00:02:11,020 So somehow this cell is able intrinsically to generate these kind of forces that are necessary. 22 00:02:11,560 --> 00:02:17,050 And clearly what must happen is that somehow all the molecules that are interacting in the system, 23 00:02:17,500 --> 00:02:21,850 um, must be able to produce these, these forces that are doing this. 24 00:02:22,090 --> 00:02:25,480 And when I talk about interacting molecules very, very quickly in the realm of, 25 00:02:25,720 --> 00:02:31,270 of chemistry, and indeed, um, as we had also heard before, now in several forms, 26 00:02:31,540 --> 00:02:41,079 um, there are processes that convert through chemical reactions, some fuel, um, into forces, um, and uh, expel um, some, some of chemical waste. 27 00:02:41,080 --> 00:02:45,340 And I will specify this, um, a bit more. Moving on. 28 00:02:45,370 --> 00:02:50,739 Um, uh, so through this talk and so what is it that, um, uh, we have to, uh, 29 00:02:50,740 --> 00:02:54,100 you know, think about when think about the physics of these biological system. 30 00:02:54,460 --> 00:03:00,850 Um, Yulia, um, had already mentioned some very important, uh, thinking that that Schrodinger has done now. 31 00:03:01,240 --> 00:03:11,380 Um, precisely, um, 80, 80 years ago, um, laying out this basic, uh, um, idea that obviously what makes living systems different from, 32 00:03:11,740 --> 00:03:16,870 uh, from, from that system is the fact, physically speaking, they're kept away from thermodynamic equilibrium. 33 00:03:17,290 --> 00:03:26,380 Um, and I want to just add here a little bit more and connect this maybe also with your undergraduate thermodynamics, um, uh, memories. 34 00:03:26,770 --> 00:03:35,140 Um, if we want to, uh, you know, keep a system out of equilibrium, one way we were taught this can be done is to what it's called a heat engine. 35 00:03:35,500 --> 00:03:38,649 And at the core of every heat engine is a temperature gradient. 36 00:03:38,650 --> 00:03:44,410 So we have a something hot. We have something called we connect this to the system that we want to study. 37 00:03:44,740 --> 00:03:50,680 And because we have this ongoing hot and cold, uh, we can sort of to work um, with, with our system. 38 00:03:50,830 --> 00:03:58,850 Okay. Now. Interesting. And the interesting thing in the biological system is that somehow everything is packed together, right? 39 00:03:58,850 --> 00:04:05,390 Because, um, there is no, um, you know, no external temperature gradient that is applied in most cases. 40 00:04:05,810 --> 00:04:13,520 Um, and in fact, it is usually not temperature that maintains these fluxes from hot to cold, um, uh, to, to extract work. 41 00:04:13,850 --> 00:04:20,180 But there are chemical reactions going on that um, in principle generate the same, uh, picture. 42 00:04:20,540 --> 00:04:23,600 And there is an analogue to temperature gradient. 43 00:04:23,820 --> 00:04:30,950 This is called the chemical potential. But all what that means is you have to, um, put energy into the system in a cell that's, 44 00:04:30,950 --> 00:04:36,290 um, nutrients, for example, that this particular cell you saw got from, from its mother. 45 00:04:36,650 --> 00:04:45,770 Um, and this allows it to, uh, so some molecular processes, um, uh, use these chemical potentials, turn it into work, turn it into forces. 46 00:04:46,770 --> 00:04:55,200 Okay. And this leads to all this fascinating, beautiful kind of self-organisation, um, that Julia and Adrian had, um, talked about. 47 00:04:56,680 --> 00:05:01,209 Now, how is this molecularly implemented? I'm also here not necessarily have to go. 48 00:05:01,210 --> 00:05:05,530 And also because Adrian had mentioned this a few times and doing that as well. 49 00:05:05,950 --> 00:05:16,720 So if we look a bit closer at the surface of the cell, what we will see in the more simplified physics picture is a polymer network, 50 00:05:16,750 --> 00:05:21,370 um, where I sort of sketch these actin this, these, uh, uh, sticks here. 51 00:05:21,370 --> 00:05:24,130 They're called actin, uh, filaments, as we heard before. 52 00:05:24,640 --> 00:05:32,799 And on these filaments, we have these very specific proteins called motor proteins that exactly do this fuel to waste conversion, um, 53 00:05:32,800 --> 00:05:37,570 by changing the confirmation of some, um, uh, molecules that are floating around, 54 00:05:37,960 --> 00:05:44,140 um, uh, and, uh, the is confirmation of change, uh, turns them from ATP into ATP. 55 00:05:44,440 --> 00:05:50,530 Um, but the point is, if you have such molecules walking on these filaments and they pull on on one end and on the other, 56 00:05:50,800 --> 00:05:56,920 they are sort of naturally able to, uh, um, um, inject forces into this, uh, into this material. 57 00:05:57,910 --> 00:06:05,080 And you can also imagine that when I have a single cell doing this, and I have now a tissue where so many of these cells are connected, 58 00:06:05,080 --> 00:06:10,300 that these forces can permeate through the tissue and generate motion also on a larger scale. 59 00:06:10,420 --> 00:06:15,790 And then you might find other mechanisms by which the strength of these forces can be controlled. 60 00:06:16,750 --> 00:06:24,160 And so what does this now look in practice? I add to the list of I hope you found beautiful movies that you have seen today. 61 00:06:24,820 --> 00:06:28,270 Um, it's, uh, organisms that we had seen before already. 62 00:06:28,270 --> 00:06:31,660 So this is, uh, zebrafish, very popular model organism. 63 00:06:32,200 --> 00:06:36,429 Um, and what you see here is the same process. Um, but it happens on the surface of a sphere. 64 00:06:36,430 --> 00:06:39,520 So we're looking on the left side from, from from here. 65 00:06:39,820 --> 00:06:43,630 The movie on the right looks at it from just from the other side. But it's the same process. 66 00:06:44,670 --> 00:06:48,180 Each white dot here is a cell. Okay. You can think of this as a cell. 67 00:06:48,840 --> 00:06:54,120 And obviously each of these cells now is undergoing this kind of cell division that you saw in the first movie. 68 00:06:54,120 --> 00:07:00,620 Just the single cell doing. And then in the same time, they are moving around and coordinating their position in space and time. 69 00:07:00,630 --> 00:07:03,870 So it's a beautiful, um, uh, process. 70 00:07:04,410 --> 00:07:08,760 And just another example to add to the list. Again, remember, 71 00:07:09,270 --> 00:07:16,710 we have a well-defined sort of molecular system in terms of what produces forces that sits in this case on the surface of an ellipsoid. 72 00:07:16,980 --> 00:07:23,180 Again, each dot here is a cell. And when we play this movie, we are looking groups. 73 00:07:23,540 --> 00:07:25,880 We are looking at the development of what is a flower beetle. 74 00:07:26,960 --> 00:07:31,520 And it has a kind of other, also an interesting geometry, but it's different than what we have seen before. 75 00:07:31,550 --> 00:07:37,760 Actually, it makes a little compartment here. And later the embryo develops inside this compartment. 76 00:07:37,760 --> 00:07:45,370 So it makes all of its own, uh, um, uh, a cavity, uh, to uh, have to snuggle in and develop. 77 00:07:45,710 --> 00:07:47,440 So I just want to make the point. Right. 78 00:07:47,450 --> 00:07:54,290 So there are a lot of ways how these files can be translated into some very interesting, um, uh, morphogenetic, um, um, processes. 79 00:07:55,450 --> 00:07:59,440 And so the question that I want to specify a little bit to what was asked before us, then, 80 00:08:00,280 --> 00:08:05,590 um, what can our physics actually, uh, contribute here to understand the development? 81 00:08:05,680 --> 00:08:14,320 Um, um, of of of of living systems. And I would alternatively titled this as maybe what's the condensed matter conundrum? 82 00:08:14,440 --> 00:08:19,660 Um, of of biology. And illustrate this with, uh, another model organism. 83 00:08:19,670 --> 00:08:28,630 Yet this is the elegance single cell embryo on the left, fully developed organism here on the right, a sort of, uh, millimetre, uh, um, long worm. 84 00:08:28,720 --> 00:08:33,940 Um, half a million or a long one. Um, and it has, as an adult, about 3000 cells. 85 00:08:34,570 --> 00:08:44,890 And what's interesting to note about this, we know almost every microscopic detail of this, uh, organism we know precisely is a genome. 86 00:08:45,610 --> 00:08:48,790 Um, of course, from humans. We also know, uh, the genome nowadays. 87 00:08:48,790 --> 00:08:53,710 But this was one of the first orders where this was actually fully, um, um, decoded. 88 00:08:54,040 --> 00:09:01,330 But we know much more than this. We know, actually, of all these 3000 cells that emerge in other organisms, exactly how they got there. 89 00:09:01,480 --> 00:09:02,620 It's very reproducible. 90 00:09:03,040 --> 00:09:14,380 We can follow and predict, uh, the position of of all of these 3000, uh, and a few cells on top of that, we know precisely it's neural network. 91 00:09:14,390 --> 00:09:21,880 So it seems like we have all the microscopic information about this organism, uh, available from single cell to final grown adult. 92 00:09:23,030 --> 00:09:27,350 And still we have no, uh, close picture here. 93 00:09:27,650 --> 00:09:33,020 That was bring us from the single cell to to such a so such a picture as an emergent, 94 00:09:33,320 --> 00:09:36,470 self-organized process as we would think of this when when we look at it. 95 00:09:36,500 --> 00:09:44,060 Okay. And I'm calling this a conundrum, the condensed matter physics conundrum, in a sense, because there had been a very influential, 96 00:09:44,360 --> 00:09:52,100 um, let's say, um, 50, 50 plus years ago, um, by Phil Anderson, who was a condensed matter that condensed matter. 97 00:09:52,130 --> 00:09:55,640 Um, uh, a physics non-equilibrium condensed matter physicist. 98 00:09:56,360 --> 00:10:04,820 And he made this point in the context back then that, uh, some people were, uh, proposing that what, what needs to be done is to understand, 99 00:10:04,850 --> 00:10:11,330 uh, the fundamental interactions of nature, uh, say particle physics as good as possible, and then we know everything. 100 00:10:11,510 --> 00:10:19,580 Okay. And he was making the point that, um, this is not exactly true, but because as soon as you have many interacting units, 101 00:10:19,940 --> 00:10:24,590 you have something called emergence and collective organisation that's that comes out of this. 102 00:10:25,010 --> 00:10:29,479 And you may actually have to think in different terms about describing these 103 00:10:29,480 --> 00:10:33,680 collective phenomena and are not able to necessarily derive them from the, 104 00:10:34,100 --> 00:10:39,560 uh, microscopic laws of your system. And that's where physics, um. 105 00:10:39,590 --> 00:10:42,860 Uh, of course, can really help biology because biology has the same issue. 106 00:10:43,100 --> 00:10:48,020 As I try to explain, um, uh, I'll convince you of with this, uh, ordinance on the top. 107 00:10:49,650 --> 00:10:54,300 And so what are the results then that that that I am, um, looking into. 108 00:10:54,510 --> 00:11:00,719 So very bluntly. So I want to understand how a cell divides, how a tissue folds. 109 00:11:00,720 --> 00:11:07,170 And of course, when I say, how do they do this from my perspective, what are the physical principles that facilitate these, these processes? 110 00:11:07,710 --> 00:11:13,860 And then taking this together, um, how this can help, uh, an organism to, to develop as a whole. 111 00:11:15,120 --> 00:11:20,910 And suddenly I'm also a theoretical. I mean, I am a full time theoretical physicist. 112 00:11:21,420 --> 00:11:29,760 Um, so what I really want to understand is what I can learn about these things using theories of of active matter. 113 00:11:30,450 --> 00:11:34,890 And then maybe more excitingly and also just this point, quite nicely, 114 00:11:35,730 --> 00:11:41,400 using biological systems to inspire our thinking about what theories of mass of active 115 00:11:41,400 --> 00:11:44,760 materials have to actually look like and what they have to be able to describe. 116 00:11:44,880 --> 00:11:51,510 Okay. And so I just sketched essentially this last box here, um, on the, 117 00:11:51,540 --> 00:11:57,780 on the slide because it's really crucial as we've hopefully cooked up already, um, up to here, 118 00:11:58,080 --> 00:12:04,440 that this work is resulting always from very close interactions between experimentalists and theorists that, 119 00:12:04,440 --> 00:12:10,370 um, have very mutually fruitful interactions. Um, or when when is interactions are mutually fruitful. 120 00:12:10,380 --> 00:12:13,950 This is mostly where the most exciting and interesting things happen. 121 00:12:16,100 --> 00:12:18,649 And so this was kind of a general introduction. 122 00:12:18,650 --> 00:12:24,340 So I want to now turn a bit more to what I, what I put into my title and want to tell you, um, what is reality. 123 00:12:24,350 --> 00:12:28,520 And maybe many of you have already heard about this, uh, for the purpose of this talk, 124 00:12:28,910 --> 00:12:35,900 what you have to think about it is think about an object that when you know it, it's just not the same object anymore. 125 00:12:36,410 --> 00:12:40,129 And this can be very nicely done. Of course, with hands we throw a hand. 126 00:12:40,130 --> 00:12:44,000 We have already we have another hand that is this metal, um, image. 127 00:12:44,210 --> 00:12:47,240 And clearly they can't fit on it. 128 00:12:47,240 --> 00:12:50,870 Other if you sort of keep the, the orientation in the same way. 129 00:12:51,380 --> 00:12:58,460 And uh, another way to say that is, um, we have in this case a broken left right symmetry because left and right, 130 00:12:58,850 --> 00:13:04,310 um, and our body and in fact, in most organisms, um, is not the same. 131 00:13:04,520 --> 00:13:08,569 Okay. And you can already ask yourself this question. 132 00:13:08,570 --> 00:13:15,560 If we start as a round cell, as an embryo that doesn't know a direction or front, a back up or down the right, left, 133 00:13:16,520 --> 00:13:23,240 uh, this must be somehow implemented because we end up all in a well-defined, um, with a well-defined morphology. 134 00:13:23,630 --> 00:13:27,980 Um, how is this symmetry breaking actually controlled and implemented in biology? 135 00:13:28,980 --> 00:13:34,610 That is why Kerala tea is in general a very interesting field to to to study in the context of facts matter. 136 00:13:34,940 --> 00:13:39,140 Um, there are many more examples. I would really say that the living world as a whole is chiral. 137 00:13:39,530 --> 00:13:44,890 Um, I just as a few examples, you know, you can look at the patterns on shells and snails. 138 00:13:44,900 --> 00:13:49,850 You know, there are like spirals. If you think about a spiral similar, it's won't be the same spiral. 139 00:13:50,150 --> 00:13:54,290 You see spiral patterns in plants. Um, also more subtle. 140 00:13:54,320 --> 00:13:55,600 So this is a cross bill. 141 00:13:56,370 --> 00:14:03,889 This is a bird that has evolved its beak to grow, uh, a bit more to the left on the top and a bit more to the right on the bottom. 142 00:14:03,890 --> 00:14:11,870 And it gives it this broad an edge over, uh, catching little backs out of, uh, narrow spaces from trees. 143 00:14:12,230 --> 00:14:15,920 Um, something I learned preparing, uh, this is this presentation. 144 00:14:16,250 --> 00:14:23,930 Um, and so if we want to link this a bit more to the research I have been doing, um, we have to get a tiny bit more technical where the reality is. 145 00:14:23,930 --> 00:14:32,239 And the systems that that is interesting for, for physics. Um, and one aspect is the Acton we had heard now several times about Acton. 146 00:14:32,240 --> 00:14:39,110 Again, this all these molecules in the, in the surface of the cell, if you look at them a bit closer, uh, these molecules are built from, 147 00:14:39,110 --> 00:14:45,620 from monomers, but they are not built as a straight stick but as a little pitch whenever a new monomers edit. 148 00:14:46,190 --> 00:14:49,130 And so you end up with something that is more like a helix. Okay. 149 00:14:49,760 --> 00:14:54,499 And the helix, just like a spiral, has sort of this notion of handedness in reality to it. 150 00:14:54,500 --> 00:14:58,670 So you have molecularly built into this cortex for reality. 151 00:14:59,090 --> 00:15:02,990 Okay. And then something I will get to later or a little bit more detail. 152 00:15:03,320 --> 00:15:06,979 This is the force generating, uh, structure. We had heard a lot about this. 153 00:15:06,980 --> 00:15:10,160 We haven't talked about um, I believe so far. 154 00:15:10,520 --> 00:15:18,349 Um. Uh, Celia. So I'm talking here about the thing about a sperm cell that must be propelled somehow through a fluid. 155 00:15:18,350 --> 00:15:19,700 So it has a little appendage. 156 00:15:20,090 --> 00:15:26,750 Um, and there is a molecular motor machinery in this appendage, and it's very similar to the one that you see in the cell. 157 00:15:27,200 --> 00:15:31,609 The net outcome is that you have a machinery that produces forces that it exerts, 158 00:15:31,610 --> 00:15:39,499 then in this case usually on surrounding fluids and is sort of propels the cell or if you are stuck somewhere, moves fluid around. 159 00:15:39,500 --> 00:15:44,780 But I will, um, show you in a bit more in a few minutes, uh, a bit more details about this case. 160 00:15:44,780 --> 00:15:50,480 So let's first look at what, um, this carnality here can do, can do for for cell. 161 00:15:51,760 --> 00:15:55,570 So remember. So what we are now looking at is again an embryo of C elegans. 162 00:15:55,900 --> 00:16:01,300 I just show you another image. Really these filaments are very clearly labelled in a specific way. 163 00:16:01,480 --> 00:16:04,520 You see this nice anisotropy, this sort of filamentous structure. 164 00:16:04,540 --> 00:16:09,670 So each of these white lines are essentially these purple and actin filaments. 165 00:16:10,270 --> 00:16:17,409 And when these miles and motors are walking across these filaments, you get a very complicated dynamics. 166 00:16:17,410 --> 00:16:22,690 Because nowadays more myosin motors, they will pull and push on actin, move the cortex around. 167 00:16:22,690 --> 00:16:26,649 And that this gives you some sort of motion dynamics. So this is still a single cell. 168 00:16:26,650 --> 00:16:29,920 And we are looking sort of on the side of the cortex. 169 00:16:31,990 --> 00:16:38,270 So this is the single cell. Now the single cell has divided. So we are now we have now one cell here and we have one cell here. 170 00:16:38,280 --> 00:16:41,590 This is after the first Division. And now something interesting happens. 171 00:16:42,010 --> 00:16:45,490 So it doesn't just divide anymore. It splits like everything we had seen so far. 172 00:16:46,000 --> 00:16:51,770 But if you look carefully when this movie starts playing, it will divide along this axis. 173 00:16:51,790 --> 00:16:54,400 Okay. This is not too, uh, not too spectacular, 174 00:16:54,730 --> 00:17:02,740 but it's actually also having motion in the top cell that goes farther to the right and motion in the lower cell that goes rather to the left. 175 00:17:03,040 --> 00:17:08,230 Okay, let's play this movie. Right. 176 00:17:08,250 --> 00:17:16,350 So you have very significant motion that again has sort of this notion of helicity, of handedness of reality. 177 00:17:16,800 --> 00:17:18,270 Um, and uh, 178 00:17:18,300 --> 00:17:26,130 the indication is here that somehow this correlative of the action that I describe gets translated here through this act of processes into, 179 00:17:26,310 --> 00:17:30,540 um, a motion specific type of motion, um, of the, of the cell. 180 00:17:31,050 --> 00:17:36,480 And what you hopefully also notice is that the division axis as it divides, it is rotating. 181 00:17:37,110 --> 00:17:44,610 So I start as a cell that essentially parallel to the left boundary of this, uh, video at the end it's somewhere lying diagonal. 182 00:17:44,700 --> 00:17:54,390 Um, in this video. Okay. And this is quite remarkable because at the beginning of the movie, you have two cells that sits along the line. 183 00:17:54,990 --> 00:18:00,480 That means all that this embryo at this time actually knows is what its front and its back will to be. 184 00:18:00,900 --> 00:18:04,440 But it doesn't know anything else. Any other direction looks the same up to this point. 185 00:18:04,620 --> 00:18:09,180 Okay. But the moment you have this kind of division and this sort of rotation, 186 00:18:09,600 --> 00:18:18,150 you're selecting a specific plane and you actually finally broke morphologically left right, up down symmetry as well, the organism. 187 00:18:18,160 --> 00:18:25,739 So that's a very clear first moment where suddenly this organism starts to have not just the front and the back, but actually also the front. 188 00:18:25,740 --> 00:18:31,930 Uh, left right, up, down. And so this is the point I just wanted to make. 189 00:18:31,940 --> 00:18:35,980 And we looked a little bit more in detail. What what is happening here? 190 00:18:36,250 --> 00:18:41,280 Um, what I want you to take away is there are cells that divide without rotating. 191 00:18:41,330 --> 00:18:45,460 Okay. So there are specific ways that we characterise this or the experimentalists characterise this. 192 00:18:45,910 --> 00:18:51,100 And there are cells that divide without um, uh, uh, tilting um, the axis. 193 00:18:51,100 --> 00:19:00,610 And the point is that this tilting of axis is very well correlated with having these counter-rotating flows that you will see on the, 194 00:19:00,790 --> 00:19:07,060 on the surface of the cell. So this is what this plot is showing. So more comfortable attending flow basically goes to the left. 195 00:19:07,540 --> 00:19:12,819 And you see the more of this we have also the more we are rotating the cells. 196 00:19:12,820 --> 00:19:19,020 So there's a very clear correlation between flows and rotations and the physics here. 197 00:19:19,030 --> 00:19:24,570 The physics question is. What are the the talks essentially in this problem that translate. 198 00:19:24,590 --> 00:19:28,700 These flows actually rotate into the rotation of the cell. 199 00:19:28,700 --> 00:19:36,680 And I spare you the details, but I tell you that what we arrived at after evaluating carefully how to talks balance in such a, 200 00:19:36,710 --> 00:19:40,640 in such a process, what we call the bulldozer model of cell annotations. 201 00:19:41,270 --> 00:19:42,800 And I'll briefly explain why. 202 00:19:43,160 --> 00:19:54,350 Um, so we arrived at a formula that says the amount of flow of this counter rotation is proportional to the rotation of the division axis. 203 00:19:54,350 --> 00:19:57,829 Okay. This is essentially what you saw in this plot. You had a more flow. 204 00:19:57,830 --> 00:20:01,340 I have two more, um, rotations. So this comes out of the the theory. 205 00:20:02,360 --> 00:20:04,430 But the physics is in this pre factor here. 206 00:20:05,030 --> 00:20:13,339 And the three factors is what I have to look at is the friction on the two sides that this dividing cell, um uh, 207 00:20:13,340 --> 00:20:19,190 is in contact with the eggshell because it's particularly in contact with the axle on two opposing sides. 208 00:20:19,640 --> 00:20:24,710 And whenever I have a difference between these frictions, this this number will be non-zero. 209 00:20:24,950 --> 00:20:28,820 And I will arrive at something that will rotate in space, its axis. 210 00:20:29,360 --> 00:20:35,480 And why do we call this a bulldozer model? Because a bulldozer that you want to rotate on a spot functions exactly the same way. 211 00:20:35,900 --> 00:20:41,300 Okay, so now the flows of the cell are represented by the motion of this chain. 212 00:20:41,840 --> 00:20:49,100 Okay. What I call here the two sides of the of the cell is basically the top of the chain and the bottom of the chain okay. 213 00:20:49,640 --> 00:20:51,770 And if a bulldozer stands on the streets, 214 00:20:51,980 --> 00:20:57,500 essentially the friction is infinite with the street and there's no friction on top because just nothing on top. 215 00:20:57,830 --> 00:21:00,680 And you see, you in this case, in this limit, this just becomes one. 216 00:21:01,070 --> 00:21:07,040 And I'm perfectly translating the motion of this chain into a rotation of this bulldozer on the spot. 217 00:21:07,400 --> 00:21:15,620 And it's this same principle that this cell now exploits to convert molecular chirality of the actin into chiral cellulose, 218 00:21:15,860 --> 00:21:24,080 into a rotation of the cell axis, which ultimately, for the first time, breaks morphologically the left right symmetry of this organism. 219 00:21:27,190 --> 00:21:31,659 And so now I move to the sort of second example of, of my research I had mentioned. 220 00:21:31,660 --> 00:21:35,470 There's this other very interesting force generating structure in biology called the Syrian. 221 00:21:35,830 --> 00:21:41,800 Um, the, the types of molecules and motor protein involved are different, but they are the same, same principle. 222 00:21:42,640 --> 00:21:44,709 And where's the reality here? 223 00:21:44,710 --> 00:21:53,950 Well, if you take a cross-section through this Syrian, what you will find is molecules arranged again in the kind of helical structural way. 224 00:21:53,950 --> 00:21:58,089 So, uh, this, this, uh, arrangement here is called the axon. 225 00:21:58,090 --> 00:22:02,440 And this goes through the whole flagella. And it also has a pitch throughout. 226 00:22:02,890 --> 00:22:06,520 So there's an inbuilt reality as well into these and archaea. 227 00:22:07,390 --> 00:22:14,380 And I'm not interested so much in a single column. But actually what you have a lot in biology are what are called cilia carpets. 228 00:22:14,680 --> 00:22:22,290 So those are structures that have different kinds of functions. Um, but they are structures where you have many, many of these beating cigar together. 229 00:22:22,390 --> 00:22:26,290 So they are all very densely packed and form these kind of carpets. 230 00:22:26,680 --> 00:22:30,700 So what we have now is a surface with a lot of cilia that beat. 231 00:22:30,700 --> 00:22:35,140 And keep in mind now this beating will have some chiral nature to it. 232 00:22:37,300 --> 00:22:40,310 And in what context? Um, ten. 233 00:22:40,600 --> 00:22:42,580 Something might just be relevant or why at all? 234 00:22:42,670 --> 00:22:49,570 Um, you know, we think this is important to, to understand how these topics are affecting flow and vice versa. 235 00:22:50,170 --> 00:22:54,340 So it is a very, um, interesting condition called CTOs and vassals. 236 00:22:54,790 --> 00:23:05,350 For anyone of you have not heard this before. So about one in 10 to 20,000 people among us have a completely mirrored internal body plan. 237 00:23:05,980 --> 00:23:10,150 So essentially all organs, everything is perfect. It's not just on another side. 238 00:23:10,480 --> 00:23:14,020 The whole morphology of everything that's internal is mirrored. 239 00:23:14,800 --> 00:23:19,780 And many of these people live a healthy life, um, and don't even notice. 240 00:23:20,170 --> 00:23:31,490 Um, but what has been found is that this is often related to a specific gene mutation in human, um, that codes for making cilia. 241 00:23:31,510 --> 00:23:31,960 Okay. 242 00:23:32,380 --> 00:23:41,590 And so the idea is here that at some point in the development, the CIA will be used to generate some kind of flow that, you know, pertains to tissue. 243 00:23:42,040 --> 00:23:47,420 And if this flow goes in the wrong direction downstream, when you arrive at the, uh, 244 00:23:47,440 --> 00:23:53,890 the new pond you have produced, um, uh, um, a human being that has a completely internal, uh, qualified. 245 00:23:54,190 --> 00:23:57,850 Okay. So we go a little bit more. 246 00:23:58,270 --> 00:24:04,020 Lo lo lo lo lo fi. Um, and look at, uh, um, starfish embryos. 247 00:24:04,030 --> 00:24:10,660 We had seen those already. Um, so because what they, they also have clear cockpits, but slightly different purpose. 248 00:24:10,930 --> 00:24:16,629 So this is a microscopic image where you see each of these little or what looks like threads that come out, 249 00:24:16,630 --> 00:24:21,220 they're all clear and they just keep beating on the surface of these little embryos. 250 00:24:21,580 --> 00:24:25,090 And what this does, it allows these embryos to swim. 251 00:24:25,540 --> 00:24:28,749 Okay. Of course, this doesn't look anything like a starfish. 252 00:24:28,750 --> 00:24:34,030 This takes quite some time to get there. It's really we are just looking at this early stage where it's somewhat benign ellipsoid. 253 00:24:34,750 --> 00:24:40,270 But the point is it can swim. And what you maybe can see already in this movie is it's not just swimming, it's also rotating. 254 00:24:40,270 --> 00:24:45,370 So it has the forward motion, but also a corkscrew aspect to it. 255 00:24:45,790 --> 00:24:49,780 And what we got interested in here is that these embryos not just swim, 256 00:24:49,960 --> 00:24:55,540 but they also quite often, uh, approach the surface of the fluid between the fluid and the air. 257 00:24:56,080 --> 00:24:59,590 And then they don't really swim, but they just keep rotating so that they, 258 00:24:59,590 --> 00:25:04,180 they maintain their rotate, the rotary aspect of the motion, but they don't really swim away anymore. 259 00:25:04,450 --> 00:25:09,940 Okay. And what was particularly cool is now if you put a lot of these embryos together, 260 00:25:10,240 --> 00:25:16,810 a lot of them come to the surface and they make these amazing, uh, what we termed living chiral crystals. 261 00:25:17,410 --> 00:25:24,040 We call them characteristics because this rotation direction here of this embryo is every time is always the same. 262 00:25:24,220 --> 00:25:27,760 So you don't have some spinning right, some left, it's always the same. 263 00:25:27,910 --> 00:25:32,559 And of course suspicion why it's always the same is again, because, you see, 264 00:25:32,560 --> 00:25:40,210 I have a hard coded handedness from the molecules that build from and accordingly, this rotation is also hard coded. 265 00:25:40,480 --> 00:25:44,830 Um, by the way, uh, and due to the fashion they are make themselves swim. 266 00:25:45,780 --> 00:25:52,620 And the idea was of this project not so much necessary to understand what's the biological meaning of this crystal formation. 267 00:25:52,920 --> 00:25:56,729 But really, we thought, this is a great opportunity to study two atoms of physics, 268 00:25:56,730 --> 00:26:01,170 because we have very good access to understand these embryos, how they are moving in the fluids. 269 00:26:01,620 --> 00:26:09,209 And so the question is, how can we understand from their properties what the properties of this emerging crystals would be? 270 00:26:09,210 --> 00:26:12,300 And if they are different from crystals that we are used to? 271 00:26:12,990 --> 00:26:17,580 Okay. And one way to, to do this, of course they are in the fluid. 272 00:26:17,590 --> 00:26:23,280 So we want to understand how the food around them moves. What you see here hopefully in this movie is they're little particles around. 273 00:26:23,280 --> 00:26:27,720 So it's a bit um, there's some, some uh yeah, some structure. 274 00:26:28,110 --> 00:26:35,820 These are little bits that are also put into the fluid. And the assumption is now that these beads move, uh, like the fluid does. 275 00:26:36,150 --> 00:26:41,760 So that means if you track the velocity of these beads, you know how the fluid moves in the surroundings. 276 00:26:41,760 --> 00:26:44,610 So this is called, uh, particle image velocity of the tree. 277 00:26:45,360 --> 00:26:53,849 And if you use that, you can get a map like this that tells you regions where the flow is very fast and regions where the flow gets slower. 278 00:26:53,850 --> 00:26:57,930 And so naturally it's fast close to the embryo, it's get slower moving, moving away. 279 00:26:59,100 --> 00:27:05,969 But what's more important is that it's now giving you immediately an idea of why at all there would be a formation of these crystals, 280 00:27:05,970 --> 00:27:09,990 because this fluid, what you see is it's drawn into the embryo from all sides. 281 00:27:10,650 --> 00:27:16,530 Now imagine you have another embryo sitting here. Naturally, it will sort of be drawn to this one embryo as well. 282 00:27:16,530 --> 00:27:23,249 And all of these embryos are doing it. And so naturally you have a mechanism to nucleate, um, uh, these kind of, um, a chrysalis. 283 00:27:23,250 --> 00:27:29,309 And there are actually also other biological systems, um, whatever that specific algae, um, that has a similar, 284 00:27:29,310 --> 00:27:34,530 uh, flow, a phonology, um, that was studied in Cambridge and in quite some detail some years ago. 285 00:27:36,220 --> 00:27:37,580 So this is a single embryo. 286 00:27:37,600 --> 00:27:43,420 When you want to understand crystal formation and the properties of a crystal, you need to understand a bit about how these embryos are interacting. 287 00:27:43,690 --> 00:27:46,900 And the simplest interaction that you can have is in a pair. Okay. 288 00:27:47,560 --> 00:27:52,960 And essentially one important thing that is happening is not just that these embryos independently spin, 289 00:27:53,710 --> 00:27:57,850 but the moment they come close to each other, they start, um, dancing around each other. 290 00:27:57,860 --> 00:28:00,040 So they're orbiting around each other. 291 00:28:01,200 --> 00:28:09,420 And qualitatively, the reason is that between them there is still some fluid, but because they are so, so much nearby and both want to rotate. 292 00:28:09,780 --> 00:28:17,400 Um, the kind of talks and forces that emerge, hydrodynamics, make them, um, uh, walk, uh, around each other. 293 00:28:18,350 --> 00:28:22,220 And studying this problem quantitatively in more detail. 294 00:28:22,550 --> 00:28:30,990 You can come up with a theoretical model of this process that captures, and in many ways, the kind of crystal formation we see in experiments. 295 00:28:31,070 --> 00:28:34,340 Now imagine this is the top view. We have disks. 296 00:28:34,370 --> 00:28:39,500 They are following the interaction rules that we have determined from the kind of experiments that I just shown you. 297 00:28:40,010 --> 00:28:44,690 Um, and the colour code here is the rotation frequency of these embryos. 298 00:28:44,690 --> 00:28:49,410 And one thing maybe to note, you see that they slow down quite a lot. 299 00:28:49,470 --> 00:28:55,160 Yeah. So they start at a rotation speed that you see by I hear a single rotation of an embryo. 300 00:28:55,160 --> 00:29:01,160 And the final crystal takes about three minutes. So you don't even see anymore that they rotate, but they still do rotate. 301 00:29:02,670 --> 00:29:07,020 And that's some nice observations that you can check that sort of to, to test your intuition in a way. 302 00:29:07,200 --> 00:29:13,020 So what I showed you here is the final state. The colour code again is the amount of rotation the speed of rotation. 303 00:29:13,990 --> 00:29:19,300 One thing, we immediately see that the, um, boundary embryos are usually faster. 304 00:29:19,390 --> 00:29:23,430 That's not so surprising. Okay, so those are embryos that have less neighbours. 305 00:29:23,440 --> 00:29:28,450 So in a sense, they have a they have a less hard time to rotate because there's less to work against. 306 00:29:28,870 --> 00:29:35,379 And this is something you will find also um, in the experiments. So you see these boundary embryos rotating much faster. 307 00:29:35,380 --> 00:29:38,980 You don't really see their, their rotation. Um, those ones are much slower. 308 00:29:40,820 --> 00:29:45,680 But then interestingly, there are also some fast ones in the middle, so you see some very bright ones here. 309 00:29:46,160 --> 00:29:51,590 If you look at the theory, what we find is that those are ones that are rather on the smaller side also makes sense. 310 00:29:51,590 --> 00:29:55,910 They have less contact with the surrounding, so it's easier for them to keep rotating. 311 00:29:56,240 --> 00:30:00,740 And that's also something you see in experiments. So here's one mark that is a bit more small, a bit smaller. 312 00:30:01,160 --> 00:30:09,470 And you see it's going quite, quite wild. Um, whereas the other ones again in the surrounding do the usual um, rather relaxing spinning. 313 00:30:10,730 --> 00:30:17,360 And then finally we have the opposite thing as well. Um, we have some here that actually rotate in the opposite direction. 314 00:30:17,540 --> 00:30:24,140 Okay. And if you look carefully, what is happening is you have some of them that are really they are large, statistically speaking large. 315 00:30:24,830 --> 00:30:31,130 And at the same time, they don't want to spin themselves too much. Now imagine this embryo in the middle doesn't want to spin at all. 316 00:30:31,340 --> 00:30:35,130 And all that happens is that the neighbouring ones are at full speed spinning. 317 00:30:35,230 --> 00:30:43,490 Okay, if you look at the interface, what they will all do. They will spin in a one in the opposite direction that is usually turning. 318 00:30:43,910 --> 00:30:48,830 Um, and this is something we see in experiments as well. So we have two examples of two pig embryos. 319 00:30:49,490 --> 00:30:54,830 And you see that they spin precisely the opposite direction of, of what other embryos, all other embryos doing. 320 00:30:55,190 --> 00:30:59,540 And so this gives us a little bit of a sense that, that we are capturing most of the physics here. 321 00:30:59,870 --> 00:31:06,790 Um, uh, in the right way. And so finally, what was about to kick off this project? 322 00:31:06,790 --> 00:31:09,640 This is sort of microscopic, how I describe the system now. 323 00:31:10,180 --> 00:31:15,040 Um, but we were wondering what what are some of the macroscopic properties of this crystal? 324 00:31:15,100 --> 00:31:21,940 Okay. So we know that, uh, you know, uh, condensed matter solids, uh, solids, um, a range of known crystals. 325 00:31:21,940 --> 00:31:26,590 We can think about their, um, emerging, uh, uh, material properties. 326 00:31:26,620 --> 00:31:34,540 Can you say something similar about these kind of crystals? And when we look at our theory in more detail, we found, um, quite a surprise. 327 00:31:34,960 --> 00:31:44,320 So back in the, um, continuum mechanics, uh, courses that that we take, we are usually told that for such an isotropic solid, 328 00:31:44,680 --> 00:31:48,909 all you need is two material parameters to describe all its properties. 329 00:31:48,910 --> 00:31:53,500 Okay. And Adrienne mentioned this, um, and that is, you know, uh, usually true. 330 00:31:53,650 --> 00:32:03,070 But what we found is that, um, our crystal somehow requires four parameters to describe in full all its elastic properties. 331 00:32:03,850 --> 00:32:12,460 So we are very carefully going back to our introduction to solids courses inspired by by my daughter. 332 00:32:13,090 --> 00:32:15,820 Um, and we found actually it's not a problem at all. 333 00:32:16,210 --> 00:32:26,170 The reason that this is allowed here is that what you what one is told about this two parameters also assumes that the system is at equilibrium, okay? 334 00:32:26,500 --> 00:32:31,750 And our crystal is not at equilibrium. We have living organisms that are pumping constantly energy into the system. 335 00:32:32,170 --> 00:32:39,220 And as a result of this, of morality and non-equilibrium nature, we are allowed to have these additional material parameters. 336 00:32:39,400 --> 00:32:43,780 And actually, um, they are referred to as elastic parameters. 337 00:32:44,470 --> 00:32:48,580 And this was a theoretical concept that not so long ago was, um, 338 00:32:48,790 --> 00:32:56,200 worked out by a group in Chicago with some beautiful physics that we could kind of find again in these, uh, living crystals. 339 00:32:57,320 --> 00:33:03,260 And then. So just finalise and end with two slides of some exciting movies and dynamics that is Christmas. 340 00:33:03,260 --> 00:33:07,460 Also take all the consequence of its complex properties. 341 00:33:08,090 --> 00:33:13,190 They spontaneously oscillate. So this is this for the crystal, 342 00:33:13,190 --> 00:33:21,230 and I hope you can see that there are some sort of large scale displacement waves that are travelling through this crystal. 343 00:33:21,740 --> 00:33:30,010 Um, uh, that, that we observed and normally again, in a normal conventional crystal, this this would not happen because this is an over time system. 344 00:33:30,020 --> 00:33:31,729 It's a very small length scale. 345 00:33:31,730 --> 00:33:41,750 But here the activity injection, this is sort of a data processed version of this um, allows these displacement waves to spontaneously pop up, 346 00:33:42,020 --> 00:33:50,390 uh, in these um, uh, in such an overtime system being a consequence of its non-equilibrium nature and being a consequence of its reality. 347 00:33:51,940 --> 00:33:54,760 And with that, I come to the conclusion. 348 00:33:55,180 --> 00:34:04,150 Um, I hope I could convince you at the beginning that active matter theory is a really powerful tool to study, uh, complex phenomena in biology. 349 00:34:04,720 --> 00:34:12,070 Um, that I showed you that chiral cortex flows, uh, translates through fiction into some morphological left right, some breaking. 350 00:34:12,460 --> 00:34:21,400 Um, and finally, um, I told you about these, uh, new living crystals that we found that have some conventional, unconventional, elastic properties. 351 00:34:21,880 --> 00:34:29,620 And I really want to thank, uh, specifically the people that were involved in this project that I talked about, uh, excellent collaborations with, 352 00:34:29,620 --> 00:34:38,320 um, uh, location, um, and, uh, the faculty group at MIT, um, and, uh, for the lab and your technical supervisor at MIT. 353 00:34:38,890 --> 00:34:45,970 Um, but then also, I want to thank the, um, Rafael Centre here in Oxford, uh, for being absolutely amazing, um, colleagues. 354 00:34:46,270 --> 00:34:51,310 And I'm happy to take any questions. I don't have postdocs to take the nasty ones, so. 355 00:34:51,340 --> 00:34:54,370 So, please. Thanks. Look.