1
00:00:13,940 --> 00:00:19,040
So, first of all, thank you very much for coming. It really is amazing to see so many people here.

2
00:00:19,040 --> 00:00:29,900
And it's great that you're interested in what we're doing. It's like this in the first week of Michaelmas term, in the first.

3
00:00:29,900 --> 00:00:40,880
And most of you are awake as well. OK, so I'm going to start from where Andrew left off and then take things in a different direction.

4
00:00:40,880 --> 00:00:47,510
I'm going to talk about what we've come to call active matter, but really, this is just physicists doing biology.

5
00:00:47,510 --> 00:00:52,790
We're looking at all sorts of different systems, we're looking at cells, we're looking at bacteria,

6
00:00:52,790 --> 00:01:01,010
and we're looking at these molecular motors that Andrew talk to you about all the way up through to larger biological systems.

7
00:01:01,010 --> 00:01:02,540
But these are too hard for us.

8
00:01:02,540 --> 00:01:12,740
So we prefer to stay and try to understand these tiny things and in particular to concentrate on the sort of things that physicists ask.

9
00:01:12,740 --> 00:01:17,930
So let me start with a sort of really broad overview of the big questions,

10
00:01:17,930 --> 00:01:22,460
and they're really the big questions which are underlying Andrews talk as well.

11
00:01:22,460 --> 00:01:26,980
And I think the first one of these is how do we work?

12
00:01:26,980 --> 00:01:34,450
Thinking of ourselves as engines, how do we actually manage to do all the things we do move around,

13
00:01:34,450 --> 00:01:42,920
but also breathe and reproduce cells and so on and.

14
00:01:42,920 --> 00:01:47,930
In the old days, the answer was you have muscles, right, and you wave your muscles around and you move.

15
00:01:47,930 --> 00:01:52,760
But now we can ask a deeper question than that because we know we're made up of cells

16
00:01:52,760 --> 00:01:58,250
and something must be happening inside the cells to get all these life processes going.

17
00:01:58,250 --> 00:02:04,100
For example, to actually make them muscles move and to move things around in the cells.

18
00:02:04,100 --> 00:02:09,470
And Andrew showed you how that's done. That's done due to these molecular motors.

19
00:02:09,470 --> 00:02:14,180
And I'm going to show you again, this beautiful movie because I like it so much.

20
00:02:14,180 --> 00:02:17,930
It's just so amazing. The first time I saw it, I said silly, isn't it?

21
00:02:17,930 --> 00:02:22,340
But it's not. This is really what's happening inside our cells.

22
00:02:22,340 --> 00:02:27,500
First of all, the cell has to lay down tracks for the motors to move along.

23
00:02:27,500 --> 00:02:32,990
That's because we're tiny here with nanoscale. And so there's a lot of Brownian motion.

24
00:02:32,990 --> 00:02:43,340
So any motor trying to just move around not being tied down is going to just get buffeted away and not be able to get anywhere.

25
00:02:43,340 --> 00:02:52,340
So you need to put down tracks and the cell is able to make these tracks and then to dissolve them again due to careful,

26
00:02:52,340 --> 00:02:55,580
really complicated and clever chemistry.

27
00:02:55,580 --> 00:03:03,680
And then the motors move along the tracks, carrying around the various proteins from one place to another in those sort of backpack things.

28
00:03:03,680 --> 00:03:14,370
This thing is like its backpack, which is the vacuum. And Andrew showed you how we're trying to make these molecular motors, and it's hard.

29
00:03:14,370 --> 00:03:21,460
The cell is amazingly good at doing this and then that's just making one of them.

30
00:03:21,460 --> 00:03:30,640
Also, you've got to control this system, it's it's a very complicated control problem, the cell has to work out, work out how to put down the tracks,

31
00:03:30,640 --> 00:03:39,490
where to put them and then to organise the motors and the vacuoles which carry things around and then work out

32
00:03:39,490 --> 00:03:46,360
how many motors it needs to pull things around and where it needs all these different sorts of proteins to go.

33
00:03:46,360 --> 00:03:54,340
It's a mind blowing problem in control theory, and Andrew showed you, even though he's doing these amazingly well, these experiments,

34
00:03:54,340 --> 00:04:01,330
it's hard to get anywhere near building one of these molecular motors that lots of them working out how they all work together.

35
00:04:01,330 --> 00:04:10,600
And so that's a really big problem. And that's one of the really big problems we want to understand because nature has evolved to do it very well.

36
00:04:10,600 --> 00:04:19,840
And if we learn how it's done, we'll be able to use these things to actually make machines and help in medicine.

37
00:04:19,840 --> 00:04:25,000
Just to show you a real picture rather than the computer simulation.

38
00:04:25,000 --> 00:04:38,500
These are these little heads here moving along the microtubule, this is like microscopy where you can actually see these things.

39
00:04:38,500 --> 00:04:45,190
So Nature sells its machines is one big question, the other one is how do you make these motors in the first place?

40
00:04:45,190 --> 00:04:49,810
And again, we heard about this. And as an example, let's look at this.

41
00:04:49,810 --> 00:04:55,100
There's a thing called the bacterial flagellum motor, which turns.

42
00:04:55,100 --> 00:05:03,260
The flagella of a bacteria, it sits here across the cell membrane, and it looks pretty much like this.

43
00:05:03,260 --> 00:05:13,100
Each of these different bits is a different protein and the sort of length scale we've got here is about 30 nanometres.

44
00:05:13,100 --> 00:05:20,690
How'd you make it? Has anyone make it? I mean, this is a computer graphics because it's a nice movie showing you how this thing might be made.

45
00:05:20,690 --> 00:05:32,600
Presumably it's built up sequentially. But you've got to take all these different proteins and you've got to put them together in the right order.

46
00:05:32,600 --> 00:05:36,740
It's called self service self-assembly, it's active self-assembly,

47
00:05:36,740 --> 00:05:42,470
because you're putting in energy, things are working out of equilibrium the whole time.

48
00:05:42,470 --> 00:05:48,290
You know, and it's just slightly mind blowing, how anybody how nature manages to do it, we can't do anything like that.

49
00:05:48,290 --> 00:05:52,340
We don't even understand how much simpler systems are put together.

50
00:05:52,340 --> 00:06:02,200
And we would like to understand it because we would like to be able to make motors this sort of size.

51
00:06:02,200 --> 00:06:11,610
OK, so that's sort of the big picture. It's the sort of picture that experiments like Andrews are starting to address.

52
00:06:11,610 --> 00:06:17,580
I want to go in a slightly different direction because we're theoretical physicists and to us,

53
00:06:17,580 --> 00:06:26,400
one of the really exciting things about this sort of system is that this active matter, biological matter is out of equilibrium.

54
00:06:26,400 --> 00:06:38,340
It's out of thermodynamic equilibrium and it's meant to stay out of thermodynamic equilibrium because otherwise you're in a bad way.

55
00:06:38,340 --> 00:06:42,810
Now you remember, presumably many of you sitting in this room that you learnt about the Boltzmann

56
00:06:42,810 --> 00:06:46,650
equation and you learnt about what happens when you have lots of particles.

57
00:06:46,650 --> 00:06:49,890
That's a statistical physics and how an equilibrium.

58
00:06:49,890 --> 00:06:57,500
You can tell that you've got the Boltzmann distribution describing things like the velocity distribution of a gas.

59
00:06:57,500 --> 00:07:03,620
That's an equilibrium system. That's what happens to a gas when it comes to thermodynamic equilibrium.

60
00:07:03,620 --> 00:07:09,590
And when you were an undergraduate, you learn a lot about equilibrium and not about much else.

61
00:07:09,590 --> 00:07:13,010
But what happens out of equilibrium?

62
00:07:13,010 --> 00:07:24,170
What happens when I take a system like this and I put together lots of active particles, lots of cells or lots of molecular motors?

63
00:07:24,170 --> 00:07:34,400
And so I'm doing statistical physics, but I'm doing statistical physics of a system which is meant to be out of thermodynamic equilibrium,

64
00:07:34,400 --> 00:07:43,190
which is continually taking energy from its surroundings, usually in the form of ATP and using it to do work.

65
00:07:43,190 --> 00:07:49,400
And that's the question that we're going to ask, and we're going to end up looking at topological defects.

66
00:07:49,400 --> 00:07:56,800
And we're going to end up finding topological defects in biological systems.

67
00:07:56,800 --> 00:07:59,380
So what sort of experimental systems have we got?

68
00:07:59,380 --> 00:08:08,030
I'm going to tell you about this experimental system, which is a very beautiful one that's been around about five years now.

69
00:08:08,030 --> 00:08:12,920
These are these molecular, these it, so these are these microtubules,

70
00:08:12,920 --> 00:08:21,600
these tracks that the molecular motors walk on and the group and Brandeis managed to isolate these tracks.

71
00:08:21,600 --> 00:08:27,320
So basically they got a big test tube full of these tracks and then they put in these molecular

72
00:08:27,320 --> 00:08:33,200
motors and these are two headed molecular motors and the motors walk along the tracks.

73
00:08:33,200 --> 00:08:39,640
So these little bits here are the feet, but they're attached to two different motors.

74
00:08:39,640 --> 00:08:41,740
These voters have a direction to them.

75
00:08:41,740 --> 00:08:47,920
So if you've got two tracks and the voters are all working in the same direction, nothing much is going to happen.

76
00:08:47,920 --> 00:08:57,280
But if this head is moving in that direction and this one is moving in that direction, it pushes these microtubules relative to each other.

77
00:08:57,280 --> 00:09:04,520
And what you're going to get is some sort of dynamics. So let's look what that dynamics looks like.

78
00:09:04,520 --> 00:09:09,200
Takes a little bit to load, this one does. There we are, you can see the of white threads.

79
00:09:09,200 --> 00:09:14,630
All these microtubules, and they're being pushed around by the molecular motors.

80
00:09:14,630 --> 00:09:19,780
And you get something which looks like turbulence. OK.

81
00:09:19,780 --> 00:09:30,680
It's not real turbulence, because here we're very small and large scales where you normally see turbulence, but it's chaotic motion.

82
00:09:30,680 --> 00:09:37,520
Let's have a look now at putting lots of another sort of active system together.

83
00:09:37,520 --> 00:09:45,510
These are bacteria that probably E. coli. So we've got lots of E. coli in a two dimensional layer.

84
00:09:45,510 --> 00:09:57,630
And again, you get something which really looks like turbulence, you get patterns, you get patterns which are larger than the individual bacteria.

85
00:09:57,630 --> 00:10:03,690
And if I plotted the vorticity field, which is basically where the flow is going this way or that way,

86
00:10:03,690 --> 00:10:10,470
what you find is you get these regions of high vorticity, red goes that way and blue goes that way.

87
00:10:10,470 --> 00:10:14,640
And this sort of scale here is about 10 bacteria across.

88
00:10:14,640 --> 00:10:22,510
So you're getting some sort of collective turbulent motion from these individual active particles.

89
00:10:22,510 --> 00:10:31,890
You seen that in other places as well. I think the next one is these are cells, these cells on a petri dish or two dimensional layer of cells.

90
00:10:31,890 --> 00:10:41,060
And if the cells just they do that, they sort of tend to move around the dish when again, you get these sort of swirling.

91
00:10:41,060 --> 00:10:43,010
Motions.

92
00:10:43,010 --> 00:10:50,840
And the reason I'm showing you lots of different systems is that I'm a theoretical physicist, and therefore it's hard to remember any one thing,

93
00:10:50,840 --> 00:10:56,330
and we want one theory which describes everything because then we can cope and if we're lucky,

94
00:10:56,330 --> 00:11:02,300
it might describe this as well, which, of course, of the beautiful patterns we see with starlings.

95
00:11:02,300 --> 00:11:06,000
This is a bit different because it's in three dimensions.

96
00:11:06,000 --> 00:11:11,480
They're moving in three dimensions, and they're not so squashed together as the other systems.

97
00:11:11,480 --> 00:11:18,160
And then I like this one. This apparent is a dolphin, was it don't know seals are a seal.

98
00:11:18,160 --> 00:11:25,430
I gave this talk in the Netherlands and they were very insistent that it was a seal and they know and it's not a shark,

99
00:11:25,430 --> 00:11:35,470
you can tell because of the surfboards, right? I was not shocked. And this thing is trying to find its dinner, and it's having trouble.

100
00:11:35,470 --> 00:11:39,340
And somehow that's some sort of collective behaviour in those fish.

101
00:11:39,340 --> 00:11:44,110
I mean, this one's a bit different, but again, you're getting this collective behaviour, these active systems,

102
00:11:44,110 --> 00:11:51,450
these living systems are behaving in a collective way in response here to some sort of perturbation.

103
00:11:51,450 --> 00:11:54,870
And I believe it's not possible to predict this.

104
00:11:54,870 --> 00:12:04,280
We don't know what's going on. OK, so this this is this is.

105
00:12:04,280 --> 00:12:11,000
What I'm going to talk about, I can't cope with the sealed and the difficult things I would get.

106
00:12:11,000 --> 00:12:18,230
OK? I wanted to try and understand this swirling state that you get.

107
00:12:18,230 --> 00:12:26,080
You get it with the bacteria and you get it with these mixtures of microtubules and molecular motors.

108
00:12:26,080 --> 00:12:36,400
And to understand it, I need to first tell you a bit about liquid crystals and topological defects that come out in liquid crystals.

109
00:12:36,400 --> 00:12:40,300
So electric crystals are as they're long, thin molecules shape,

110
00:12:40,300 --> 00:12:47,350
which is long and thin and at high temperatures, they just order random weather in order a tool.

111
00:12:47,350 --> 00:12:53,740
They just point in random directions. If you call them down, they form a pneumatic state.

112
00:12:53,740 --> 00:13:01,330
A democratic state is one where the molecules all point in more or less the same direction.

113
00:13:01,330 --> 00:13:05,930
So there's what we call orientation or Lowder, but no positional order.

114
00:13:05,930 --> 00:13:13,810
They're not on a lattice. The reason they do that is just then they increase their entropy, they have more space.

115
00:13:13,810 --> 00:13:18,730
Now we know about this in Oxford, right, because of high temperatures in the summer.

116
00:13:18,730 --> 00:13:29,200
You get an isotropic phase and at low temperatures in the winter you get a pneumatic phase.

117
00:13:29,200 --> 00:13:31,300
These secret crystals are really important.

118
00:13:31,300 --> 00:13:39,850
They are in all the display screens that have display screens work because of the way they interact with light.

119
00:13:39,850 --> 00:13:48,850
And one of the problems, if you're doing display screens, is that you can get topological defects in these liquid crystals.

120
00:13:48,850 --> 00:13:57,070
Places where the ordering wire this alignment goes wrong, they're called topological defects,

121
00:13:57,070 --> 00:14:04,180
because if you want to untwist this, you actually have to move everything all the way out to infinity.

122
00:14:04,180 --> 00:14:16,470
It actually mucks up the order everywhere. This shape here is called a plus a half defect, or I think we call this one a comet defect.

123
00:14:16,470 --> 00:14:22,230
This one here is a minus a half defect. It's the only ones we're going to have to think about, OK,

124
00:14:22,230 --> 00:14:29,040
places where the ordering goes wrong and normally what will happen in a in a normal

125
00:14:29,040 --> 00:14:35,520
liquid crystal is that the plus two halves and the minus the halves behave like charges.

126
00:14:35,520 --> 00:14:41,790
They move towards each other and they destroy each other because they want to minimise their energy.

127
00:14:41,790 --> 00:14:46,170
You really don't like having these guys, and so they move towards and they destroy each other.

128
00:14:46,170 --> 00:14:51,720
And if you're lucky in a perfect liquid crystal, they will inil out.

129
00:14:51,720 --> 00:15:05,280
But in an imperfect one, what happens is they get stuck on basically dirt in the liquid crystal, and then they muck up how good they are as screens.

130
00:15:05,280 --> 00:15:09,390
This sort of logical defects are all over the place.

131
00:15:09,390 --> 00:15:16,020
Biology was until recently the only place they weren't really are meant to be important in the early universe.

132
00:15:16,020 --> 00:15:21,210
There, certainly you would have seen as undergraduates their importance is crystal dislocations,

133
00:15:21,210 --> 00:15:28,080
and a lot of the recent work in Hard Condensed Matter has been interested in these defects.

134
00:15:28,080 --> 00:15:33,900
We wanted them to be in biology as well.

135
00:15:33,900 --> 00:15:42,270
So let's go back and have another look at this, that's my suspension of my swimmers, this is the sort of state that you get.

136
00:15:42,270 --> 00:15:48,150
And these things are pneumatic right there, long and thin, so you might expect some sort of pneumatic properties.

137
00:15:48,150 --> 00:15:52,170
So we did a simulation of this and we asked, Let's have a look at it.

138
00:15:52,170 --> 00:15:56,760
Let's actually look at the top of logical defects and see what they do.

139
00:15:56,760 --> 00:16:07,360
So what I'm going to show you now is a simulation of this basically this sort of vorticity field with the topological defects on it.

140
00:16:07,360 --> 00:16:16,810
OK, the red ones are these plus I have defects and the blue ones are the minus a half defects, and I think those guys are going to do the right thing.

141
00:16:16,810 --> 00:16:22,450
They never did. The ones I want to look at, OK. They annihilate in pairs, which they're meant to do.

142
00:16:22,450 --> 00:16:29,290
OK, but then just look here. They're created in pairs.

143
00:16:29,290 --> 00:16:33,940
All right. I'll give you just pair to get in a minute.

144
00:16:33,940 --> 00:16:40,060
OK, if you look carefully, you'll see them disappearing, which is what we expected, there's one there,

145
00:16:40,060 --> 00:16:46,990
but the number isn't decreasing, and that's because they're also popping out and being created.

146
00:16:46,990 --> 00:16:54,760
And that's what makes these out of equilibrium systems, these active systems, these biological systems different,

147
00:16:54,760 --> 00:17:04,550
that you can have a sort of gas of these topological defects, which are continually being destroyed and then reformed.

148
00:17:04,550 --> 00:17:11,690
It's the energy that you're pumping in, which allows them to be formed, and then what happens is in a passive system,

149
00:17:11,690 --> 00:17:17,300
you know, by thermal fluctuation, you might get a pack, but then they'll destroy each other immediately.

150
00:17:17,300 --> 00:17:26,630
What happens in these active systems if a pair is formed? They say they actually move because of the stresses on them because of this activity.

151
00:17:26,630 --> 00:17:34,130
They move away from each other and in particular the plus a half once a motile and move quickly away.

152
00:17:34,130 --> 00:17:39,080
And the minus a half ones aren't maritime time. They tend to stay there. That's just because of their symmetry, really.

153
00:17:39,080 --> 00:17:45,700
Because these are asymmetric, they don't move anywhere. And so they're able to escape from each other.

154
00:17:45,700 --> 00:17:50,650
And I think I've got a slide which shows the velocity field around these things.

155
00:17:50,650 --> 00:17:58,210
This one here has a velocity field with two loops, and it moves in this direction.

156
00:17:58,210 --> 00:18:06,910
This one here actually has a velocity field with six loops in it.

157
00:18:06,910 --> 00:18:12,620
Let's look at the experiments again and see if we can actually see these things in real experiments,

158
00:18:12,620 --> 00:18:21,700
let's look at these experiments where I had the microtubules driven by molecular motors.

159
00:18:21,700 --> 00:18:27,940
And you'll see an arrow. Red Arrow after the plus a half defect, blue after the minus a half.

160
00:18:27,940 --> 00:18:30,280
So these turn out to be defective.

161
00:18:30,280 --> 00:18:34,810
I know it's I've got to still in a minute because it's really hard to see them until you've been looking at them lots.

162
00:18:34,810 --> 00:18:40,600
But we will look at the dynamics. Basically, these things fold over and form defects.

163
00:18:40,600 --> 00:18:50,470
You can sort of see that the three fold symmetry, sometimes at the minus one's.

164
00:18:50,470 --> 00:18:57,220
And if it worries you, which I think it might, right, this is a still this is evolving with time.

165
00:18:57,220 --> 00:19:01,880
These are the microtubules. They sort of bend over and they make this.

166
00:19:01,880 --> 00:19:06,460
You can see that this thing has the shape of a plus a half defect.

167
00:19:06,460 --> 00:19:14,070
And this thing has this shape. Of a minus a half defect.

168
00:19:14,070 --> 00:19:23,580
OK, so people have looked at these, they've looked at their properties. They pretty much understand how this defects drive this active turbulence.

169
00:19:23,580 --> 00:19:28,740
There isn't really a theory of what's going on here. That's still to come.

170
00:19:28,740 --> 00:19:37,280
All right. There's an understanding, but there's not what theoretical physicists would call a theory.

171
00:19:37,280 --> 00:19:50,850
So. Let's do the biology now, just in case there are any.

172
00:19:50,850 --> 00:19:58,260
This is just just in case there are any biologists in the audience, I can never remember the right words,

173
00:19:58,260 --> 00:20:06,780
the right biologists are really good at remembering things and they mind when you say it wrong, so I'm afraid this is the best we can do.

174
00:20:06,780 --> 00:20:11,280
We're looking at generic properties here. I do my best.

175
00:20:11,280 --> 00:20:23,780
So so. Two, two stories I'm going to tell you, if I've got time where we actually find topological defects in real biological systems.

176
00:20:23,780 --> 00:20:29,730
And. Then in both cases, they actually do something.

177
00:20:29,730 --> 00:20:36,150
They have a biological relevance. And this is all very new people only sort of.

178
00:20:36,150 --> 00:20:38,480
Well, we found this stuff a couple of years ago.

179
00:20:38,480 --> 00:20:46,080
OK, well, let's not even and some certainly the first part of the work I'm going to show you is is published.

180
00:20:46,080 --> 00:20:52,140
And so it really is very new research and you'll see that these are really rather model systems,

181
00:20:52,140 --> 00:20:58,640
but maybe these defects are important in real medical systems as well.

182
00:20:58,640 --> 00:21:07,800
The jury is out. So I'm going to start with these bacteria, the cake, and these bacteria pretty obviously have pneumatic symmetry.

183
00:21:07,800 --> 00:21:15,960
All right. We're going to look at how to write this name down this one Pseudomonas, which is one of the official sorts of bacteria.

184
00:21:15,960 --> 00:21:21,390
These things crawl. I'm looking at them. They're meant to crawl if a move is going to work.

185
00:21:21,390 --> 00:21:27,840
Yes, they will. All right. They're moving in a two dimensional layer on a surface.

186
00:21:27,840 --> 00:21:33,160
This is the sort of thing you'd see prior to biofilm formation.

187
00:21:33,160 --> 00:21:40,540
They pretty obviously look like this liquid crystals, they have pneumatic symmetry, they have this head tail symmetry.

188
00:21:40,540 --> 00:21:48,970
They move by having little legs, so they sort of walk along the surface on these little legs, which pull them along.

189
00:21:48,970 --> 00:21:53,170
OK, it's called twitching mobility, and it doesn't actually matter much,

190
00:21:53,170 --> 00:22:01,360
but they do change direction, so their motion is pneumatic as well, moving in both directions.

191
00:22:01,360 --> 00:22:06,860
OK, so maybe we can find topological defects in this system. I mean, the right shape.

192
00:22:06,860 --> 00:22:16,340
All right. And there they are, these are the topological defects, the red ones are the plus ones which are moving the blue ones of the minus ones,

193
00:22:16,340 --> 00:22:23,750
which are not self-propelled, they're only moving when the rest of the bacteria drags them along.

194
00:22:23,750 --> 00:22:30,500
And just to check, because we do lots of modelling, we wanted to do a model of these.

195
00:22:30,500 --> 00:22:38,990
So we did the very simplest model you can think of. We had a load of rods in our computer and we just gave them a velocity, so they moved.

196
00:22:38,990 --> 00:22:42,800
And when they hit each other, we had a repulsive interaction so they didn't overlap.

197
00:22:42,800 --> 00:22:47,190
So rods, which can't overlap, moving around.

198
00:22:47,190 --> 00:22:53,460
This is what happens if you do that here with the rods, they're moving, they're repelled by the other rods.

199
00:22:53,460 --> 00:22:59,460
And again, you can see the defects, the topological defects, OK?

200
00:22:59,460 --> 00:23:13,150
You can get the computer to find those for you. Now, it seems a very reasonable question to ask.

201
00:23:13,150 --> 00:23:20,020
You know, are they really like the topological defects we saw before that these are places where you know,

202
00:23:20,020 --> 00:23:28,060
you can you can define the idea of a topological defect, but did the same thing as we are seeing as we're used to from the liquid crystals.

203
00:23:28,060 --> 00:23:35,930
Are they the same in this simple model? And in the real bacteria and in the simulations I showed you to start with?

204
00:23:35,930 --> 00:23:44,150
And so what we did is we measured the velocity field in all the different sorts of models and the simulations.

205
00:23:44,150 --> 00:23:53,970
And here's the answer for the velocity field. This is what I showed you before around a plus a half defect, two loops.

206
00:23:53,970 --> 00:24:03,280
Here is what happens around a minus a half defect, and you get these six loops.

207
00:24:03,280 --> 00:24:09,120
This is what happens in that model of rods. Same thing, but it's a bit more noisy.

208
00:24:09,120 --> 00:24:14,220
This is what happens in the experiments. Same thing again.

209
00:24:14,220 --> 00:24:21,480
It's a lot more noisy because these are real experiments on real things, but for all the logical experiments, this is amazingly good agreement.

210
00:24:21,480 --> 00:24:27,560
OK? You can see those six loops. So we're seeing the same thing.

211
00:24:27,560 --> 00:24:40,530
This is really very strong evidence that we're seeing the same sort of thing in these bacterial layers and in sort of theoretical models.

212
00:24:40,530 --> 00:24:46,560
OK, so the reason we got to this was that we,

213
00:24:46,560 --> 00:24:58,620
as zoologist colleagues and people in zoology were interested in what happens when you have different strains of bacteria which are mixed together.

214
00:24:58,620 --> 00:25:04,470
So the question was to mix two different strains of bacteria here blue and yellow.

215
00:25:04,470 --> 00:25:06,630
But I'll tell you what those are in a minute.

216
00:25:06,630 --> 00:25:15,470
And to see how they expanded because bacteria like expanding, that's one of their rationales for being is to invade places.

217
00:25:15,470 --> 00:25:21,570
OK, so you put them on the surface and you look how they expand as they divide.

218
00:25:21,570 --> 00:25:26,790
So they expand partly because they're dividing and partly because they're motile.

219
00:25:26,790 --> 00:25:30,780
And to understand this story, you have to think of the hair in the tortoise.

220
00:25:30,780 --> 00:25:42,460
OK, this is a hair in the tortoise story and the bacterial world. So the two different sorts of bacteria that were mixed together is, first of all,

221
00:25:42,460 --> 00:25:50,770
the wild type Pseudomonas and what the biologists mean when they say wild type is ones that they haven't looked around with.

222
00:25:50,770 --> 00:25:56,950
The way they mucked around with some of them is they made these things called delta pillage.

223
00:25:56,950 --> 00:26:01,310
And what they did, though, is add more feet. So they did genetic modification.

224
00:26:01,310 --> 00:26:06,760
So these things had more of these feelers. And so they moved faster.

225
00:26:06,760 --> 00:26:13,840
So they had two populations. The brown population had this is the velocities that they had.

226
00:26:13,840 --> 00:26:25,450
The brown population had high of high velocities and the blue population had lower velocities.

227
00:26:25,450 --> 00:26:30,280
So I think I might have got the colours wrong, but never mind. These are the wild type.

228
00:26:30,280 --> 00:26:37,570
These are the guys that just slow. These are the ones with more feet that are fast.

229
00:26:37,570 --> 00:26:42,890
And the colon is expanding. In this direction.

230
00:26:42,890 --> 00:26:53,510
OK, slogans at the top is the colony expanding. OK.

231
00:26:53,510 --> 00:26:59,670
So this is very strong evidence. That the slower ones.

232
00:26:59,670 --> 00:27:07,380
They start off slow, but then they expand faster. Exactly the hair in the toe Toy Story, these lines, everybody worries about these lines.

233
00:27:07,380 --> 00:27:11,410
That's just because you have to move the stage of the microscope. All right. And there's no cheating.

234
00:27:11,410 --> 00:27:15,770
You don't sort of wait in one of them to let men get faster. Yes.

235
00:27:15,770 --> 00:27:25,200
OK. So why why are these slower bacteria moving faster?

236
00:27:25,200 --> 00:27:29,190
This is more evidence for the same thing. All right.

237
00:27:29,190 --> 00:27:34,050
The yellow ones are the first ones.

238
00:27:34,050 --> 00:27:39,840
If you look at the edge of the colony to start with, the yellow ones win.

239
00:27:39,840 --> 00:27:54,750
But later on, as the colony gets denser. Somehow, the yellow ones aren't there, and it's the blue ones which are spreading the slow ones and moving.

240
00:27:54,750 --> 00:27:59,260
OK, so why we've got to answer why.

241
00:27:59,260 --> 00:28:09,810
Well, this is a picture of the inside of the colony and experimental picture, and what you can see is you get sort of blobs forming.

242
00:28:09,810 --> 00:28:15,120
And these blobs are stationary. The movie sort of stops when they become stationary.

243
00:28:15,120 --> 00:28:22,290
You can see that the stationary blob says somehow you're getting blobs forming.

244
00:28:22,290 --> 00:28:31,710
And it turns out that these blobs tend to be mostly made up of the faster bacteria.

245
00:28:31,710 --> 00:28:43,860
Those blobs are places where the bacteria, instead of moving around horizontally on the surface form clusters, which are pointing upwards.

246
00:28:43,860 --> 00:28:47,430
Places where they basically form pointing upwards.

247
00:28:47,430 --> 00:28:55,600
Clusters which are stuck. We call it vertical ization, but at such a horrible word, I really didn't like saying it.

248
00:28:55,600 --> 00:29:02,920
All right. Clusters where they're stuck, clusters where biofilms will start to fall.

249
00:29:02,920 --> 00:29:07,860
And for some reason, that happens with the first ones, but not for the slow ones.

250
00:29:07,860 --> 00:29:14,850
And so the fast ones get stuck in these sticking up clusters and the slow ones are left to expand.

251
00:29:14,850 --> 00:29:20,310
So we've moved the question to how are these stacking up clusters formed?

252
00:29:20,310 --> 00:29:30,520
And the answer is because of topological defects. What happens is that these plus a half defects by chance.

253
00:29:30,520 --> 00:29:34,460
Two of them are moving towards each other.

254
00:29:34,460 --> 00:29:45,260
Two plus a half defects moving towards each other form a virtual plus one defect and start moving around each other.

255
00:29:45,260 --> 00:29:58,630
As they move around each other, a combination of energies and the momentum pushes these guys up so that they stick out of the plane.

256
00:29:58,630 --> 00:30:04,450
It's a reasonably slowly moving towards each other, which would happen for the Slovak teria.

257
00:30:04,450 --> 00:30:10,060
What happens is the defects come in. You get things standing up on end.

258
00:30:10,060 --> 00:30:16,810
But there isn't enough energy to form you to really nucleating a standing up cluster.

259
00:30:16,810 --> 00:30:25,790
They join together and they fall back down again. Whereas for the fast ones, what happens is you get this standing up cluster formed.

260
00:30:25,790 --> 00:30:33,470
And then my simulation box isn't big enough, but then it keeps growing.

261
00:30:33,470 --> 00:30:40,760
So the first ones confirmed the vertical clusters and the slow ones Kong.

262
00:30:40,760 --> 00:30:47,050
This is a picture of it actually happening in a real system, but it's a bit hard to see.

263
00:30:47,050 --> 00:30:53,630
Again. This is a real experiment. Very clever experiment you can just about see it happening.

264
00:30:53,630 --> 00:30:58,820
And here is instead still of the same thing. Here is the region where they're standing up on end.

265
00:30:58,820 --> 00:31:04,880
You can see they're the end of them or here, perhaps from the side, it's easier to see they're standing up on end,

266
00:31:04,880 --> 00:31:13,010
and they tend to be the first bacteria which join together in these clusters.

267
00:31:13,010 --> 00:31:17,870
So then we did another simulation just to really say the same thing, just to check.

268
00:31:17,870 --> 00:31:27,620
We put fast and slow together. You can see the standing up clusters forming.

269
00:31:27,620 --> 00:31:36,520
And you can count the number of fast and slow bacteria in these clusters, which is standing on end, which are stuck.

270
00:31:36,520 --> 00:31:41,530
And you find that many more of the first bacteria in there.

271
00:31:41,530 --> 00:31:50,330
And so that leaves the slow ones to be able to spread. And remember, what started off those clusters was the topological defects.

272
00:31:50,330 --> 00:32:03,120
It's because you've got problems for defects in these systems that you can get this nucleation of of things which are standing up on end.

273
00:32:03,120 --> 00:32:11,400
OK, so that's the hair in the tortuous story. What we actually did first, which was stupid, because it's much harder.

274
00:32:11,400 --> 00:32:22,360
Was to look at topological defects in a different sort of cell in these eukaryotic cells, so these are cells which line your stomach.

275
00:32:22,360 --> 00:32:30,910
Indeed, pretty much all the surfaces of your body, so they're meant to be in two dimensions, more or less.

276
00:32:30,910 --> 00:32:39,310
OK. And what people do is take them out and cultured them and put them on petri dishes.

277
00:32:39,310 --> 00:32:44,760
So you have two dimensional layers of cells.

278
00:32:44,760 --> 00:32:53,760
Now, it's much less obvious that these things are anything to do with these pneumatics with topological defects because they're the wrong shape,

279
00:32:53,760 --> 00:33:05,180
they're circular. So what actually happens here is what we did is we looked at these cells, and as they move, they tend to get pulled.

280
00:33:05,180 --> 00:33:14,960
And so instantaneously they do have a long axis. So we took that long axis and we put a line along it.

281
00:33:14,960 --> 00:33:22,780
And that made it look like a dramatic. And then we looked for topological defects.

282
00:33:22,780 --> 00:33:30,230
And in fact, you can identify topological defects in these systems.

283
00:33:30,230 --> 00:33:39,350
This is one of these +1 ones, and you can see that it's moving, which is what the plus sorry plus half ones are meant to do.

284
00:33:39,350 --> 00:33:50,510
And you can measure the velocity field around it and it looks the same. And so these these guys really are topological defects.

285
00:33:50,510 --> 00:33:57,030
One of my favourite experiments is this one.

286
00:33:57,030 --> 00:34:05,550
What happened here is that we measured that we counted the number of these topological defects in one of these cell layers.

287
00:34:05,550 --> 00:34:12,480
And then the experimentalist administered something called Blaby Statine to these cells.

288
00:34:12,480 --> 00:34:19,200
And what bleb is starting is if you're a cell is basically a sleeping pill, so it puts them to sleep.

289
00:34:19,200 --> 00:34:23,340
And so if they're asleep, they're not moving, they're not being active,

290
00:34:23,340 --> 00:34:29,010
they're not behaving as an active system, and they're not creating topological defects.

291
00:34:29,010 --> 00:34:33,630
So you expect the defects to slowly aneel out.

292
00:34:33,630 --> 00:34:43,820
And that's exactly what they're doing. This is, the number of defects goes down with time because the cells have stopped moving.

293
00:34:43,820 --> 00:34:51,950
Then you get to hear and what happens here is that the destruction is washed out.

294
00:34:51,950 --> 00:35:01,700
So basically it's an alarm clock and the cells wake up again. If the cells wake up, then the number of defects starts to increase.

295
00:35:01,700 --> 00:35:12,890
And you end up with, I think, quite nice evidence that the activity in these systems is creating topological defects.

296
00:35:12,890 --> 00:35:18,560
So that's fun. Is there any biology going on here?

297
00:35:18,560 --> 00:35:28,850
Well, what we found is a correlation between the position of these defects and places where the cells die.

298
00:35:28,850 --> 00:35:38,000
So here's my cell layer. And what happens is this in these layers, you get cells which die and are pushed out of the layer.

299
00:35:38,000 --> 00:35:46,820
This is a perfectly normal thing because new cells are being created all the time and you need to keep the density of cells constant.

300
00:35:46,820 --> 00:35:52,820
It's called apoptosis. It's just dead cells being removed from the layer.

301
00:35:52,820 --> 00:36:03,640
We found that the places where the apoptosis occurs is related to the position of the topological defects.

302
00:36:03,640 --> 00:36:12,070
This is a biological result, so the correlation is not 100 percent, but it was pretty strong, strong enough that we believe it.

303
00:36:12,070 --> 00:36:16,910
And actually, there's a mechanism why that might happen.

304
00:36:16,910 --> 00:36:24,230
As a physicist, my thought was right topological defects are regions where everything's ordered in the wrong way.

305
00:36:24,230 --> 00:36:26,900
That's a position of high stress.

306
00:36:26,900 --> 00:36:35,270
And so it's sensible that this is why the cells get miserable and they die off and then they're pushed out of the layer.

307
00:36:35,270 --> 00:36:38,390
It's sort of like that, but life is a bit more tricky.

308
00:36:38,390 --> 00:36:48,100
And biologists and what my very clever biologist colleagues worked out was that actually what happens is if you do have regions of high stress.

309
00:36:48,100 --> 00:36:55,420
A protein called Yap is expressed, and it's moved from the nucleus to the cytoplasm.

310
00:36:55,420 --> 00:37:04,150
So this Yap thing is a chemical signal. And this is a chemical signal why cells die and you can show that at the top of logical defects,

311
00:37:04,150 --> 00:37:08,890
because of the stress, the Yap moves from the nucleus to the cytoplasm.

312
00:37:08,890 --> 00:37:17,200
And that's what kills the cells. And once they're dead, they're ejected from the monolayer.

313
00:37:17,200 --> 00:37:30,200
OK, so I've shown you. To places where you end up with topological defects, actually doing something in biology.

314
00:37:30,200 --> 00:37:37,990
They say it's only I think it was about 18 months ago. This was first started this research.

315
00:37:37,990 --> 00:37:42,130
So there's an awful lot for biological systems out there to look at.

316
00:37:42,130 --> 00:37:48,440
And that's what we're busy doing at the moment and in particular.

317
00:37:48,440 --> 00:37:55,880
The reason we can do this research is because we have such amazing graduate students and postdocs here.

318
00:37:55,880 --> 00:38:00,800
The people most responsible for this work is Ali and Ahmed.

319
00:38:00,800 --> 00:38:06,410
But another list of other students, postdocs and colleagues that have collaborated.

320
00:38:06,410 --> 00:38:14,420
And the other thing I'm going to say is that pretty much none of these people are British, and I think that's brilliant.

321
00:38:14,420 --> 00:38:19,550
Theoretical physics is somewhere where people from all over the world can come to the

322
00:38:19,550 --> 00:38:25,490
UK and we can be friends and we can give Connexions which are going to happen forever.

323
00:38:25,490 --> 00:38:32,330
For example, Armin is from Iran. And that's one of the really nice reasons for being a theoretical physicist.

324
00:38:32,330 --> 00:38:38,464
Thanks very much, Alison.