1 00:00:16,750 --> 00:00:22,060 ADAM MARTIN: So, last semester, my grandfather passed away, 2 00:00:22,060 --> 00:00:28,000 and I was responsible for explaining to my two sons 3 00:00:28,000 --> 00:00:31,210 how a funeral works. 4 00:00:31,210 --> 00:00:32,619 So I'm a professor, right? 5 00:00:32,619 --> 00:00:36,220 I pride myself on being able to explain things clearly. 6 00:00:36,220 --> 00:00:39,880 So I went to tell my five-year-old son 7 00:00:39,880 --> 00:00:42,220 sort of what's going on during the funeral. 8 00:00:42,220 --> 00:00:47,375 I told him, your papa's body is up in that wooden box up there. 9 00:00:47,375 --> 00:00:49,000 We're going to celebrate him right now. 10 00:00:49,000 --> 00:00:51,070 We're going to go to the cemetery, 11 00:00:51,070 --> 00:00:53,760 and then we're going to bury him. 12 00:00:53,760 --> 00:00:55,960 And you know, I'm a professor. 13 00:00:55,960 --> 00:00:58,390 I thought I nailed it, OK? 14 00:00:58,390 --> 00:01:01,000 Except my son was showing this looking 15 00:01:01,000 --> 00:01:02,890 look of concern in his eyes. 16 00:01:02,890 --> 00:01:03,790 And he looked at me. 17 00:01:03,790 --> 00:01:06,940 He was like, what about his head? 18 00:01:06,940 --> 00:01:11,320 So my plea for this semester is please let me 19 00:01:11,320 --> 00:01:14,815 know when I've forgotten the part about the head, OK? 20 00:01:14,815 --> 00:01:16,440 You know, you guys are listening to me. 21 00:01:16,440 --> 00:01:18,160 I might have forgotten something that, 22 00:01:18,160 --> 00:01:21,670 to me, seems kind of obvious, but that, for you, it 23 00:01:21,670 --> 00:01:25,600 would help to know to understand the material. 24 00:01:25,600 --> 00:01:28,930 So today, we're going to start with cells. 25 00:01:28,930 --> 00:01:33,190 And so here, you can see this is one of my favorite movies. 26 00:01:33,190 --> 00:01:37,000 This is a neutrophil cell here that's migrating. 27 00:01:37,000 --> 00:01:39,010 You can see it's chasing after this smaller 28 00:01:39,010 --> 00:01:42,040 cell which is a bacteria cell. 29 00:01:42,040 --> 00:01:45,125 And around this neutrophil, what you're seeing here 30 00:01:45,125 --> 00:01:46,750 are these red blood cells, which aren't 31 00:01:46,750 --> 00:01:50,380 doing very much of anything. 32 00:01:50,380 --> 00:01:52,990 So the point I'm making with this video 33 00:01:52,990 --> 00:01:58,330 is that cells have a huge amount of diversity. 34 00:01:58,330 --> 00:02:00,100 So cells have diversity. 35 00:02:04,930 --> 00:02:10,460 As you can see from the video, there's a diversity in size. 36 00:02:10,460 --> 00:02:15,035 There's diversity in shape and also diversity in behavior. 37 00:02:22,970 --> 00:02:25,070 OK, so we're going to unpack this a little bit. 38 00:02:25,070 --> 00:02:29,110 And I just want to start by just pointing out 39 00:02:29,110 --> 00:02:32,050 that until now in the semester, we've dealt mainly 40 00:02:32,050 --> 00:02:37,390 with very small things, such as atoms, small molecules, lipids, 41 00:02:37,390 --> 00:02:38,650 and proteins. 42 00:02:38,650 --> 00:02:41,410 And the size of these structures, they're 43 00:02:41,410 --> 00:02:43,870 on the nanometer scale. 44 00:02:43,870 --> 00:02:46,585 Now, cells are a unit up in size. 45 00:02:49,390 --> 00:02:54,520 Cells span several orders of magnitude in size. 46 00:02:54,520 --> 00:02:56,770 So bacterial cells are on the small side. 47 00:02:56,770 --> 00:03:00,970 They're on the 1 micron to 10 micron size. 48 00:03:00,970 --> 00:03:02,290 So you can see that here. 49 00:03:02,290 --> 00:03:06,340 Most bacteria is about 1 micron to 10 micron. 50 00:03:06,340 --> 00:03:11,170 But our cells span from tens of microns to hundreds of microns, 51 00:03:11,170 --> 00:03:15,490 and even larger than that, because the human egg 52 00:03:15,490 --> 00:03:18,120 is on the order of a millimeter in size. 53 00:03:18,120 --> 00:03:20,120 This is not a human egg, but this is a frog egg. 54 00:03:20,120 --> 00:03:23,560 You can see often the egg cells are the biggest of all cells. 55 00:03:23,560 --> 00:03:26,470 The biggest cell is an ostrich egg. 56 00:03:26,470 --> 00:03:29,440 It's about 15 centimeters, I believe. 57 00:03:29,440 --> 00:03:35,238 So cells span a huge, wide range of sizes. 58 00:03:35,238 --> 00:03:37,030 I'm going to start with the simplest, which 59 00:03:37,030 --> 00:03:38,770 is a bacteria cell. 60 00:03:38,770 --> 00:03:41,230 And what I want to point out about this cell 61 00:03:41,230 --> 00:03:43,150 is its simplicity. 62 00:03:43,150 --> 00:03:46,990 So here, you can see this is an electron micrograph 63 00:03:46,990 --> 00:03:49,160 of bacterial cell here. 64 00:03:49,160 --> 00:03:51,160 And this is a cartoon just illustrating 65 00:03:51,160 --> 00:03:52,900 some of the key features. 66 00:03:52,900 --> 00:03:56,540 You have a plasma membrane and a cell wall. 67 00:03:56,540 --> 00:04:00,750 The cell wall here is in sort of-- the periplasmic space 68 00:04:00,750 --> 00:04:02,320 is in green. 69 00:04:02,320 --> 00:04:05,440 And this encapsulates the cytoplasm. 70 00:04:05,440 --> 00:04:07,690 And the only other real structure you can see, 71 00:04:07,690 --> 00:04:12,440 in this case, is this nucleoid structure in the middle. 72 00:04:12,440 --> 00:04:13,975 And what the nucleoid is, is it's 73 00:04:13,975 --> 00:04:16,300 just the chromosome of the bacterium. 74 00:04:19,120 --> 00:04:21,700 And I want to point out that later on in the course, 75 00:04:21,700 --> 00:04:26,850 Professor Imperiali is going to come back and tell you 76 00:04:26,850 --> 00:04:29,890 about antibiotics and how bacteria can develop 77 00:04:29,890 --> 00:04:33,580 antibiotic resistance, which is of critical importance 78 00:04:33,580 --> 00:04:38,080 for biology and medicine. 79 00:04:38,080 --> 00:04:41,280 So our cells are more complicated than this. 80 00:04:41,280 --> 00:04:43,920 And that's because if you look at this EM here, 81 00:04:43,920 --> 00:04:45,930 you can see that eukaryotic cells-- 82 00:04:45,930 --> 00:04:47,900 and we are eukaryotes-- 83 00:04:47,900 --> 00:04:50,840 have membrane-bound compartments. 84 00:04:50,840 --> 00:04:54,900 There's a nucleus here that houses our nuclear DNA. 85 00:04:54,900 --> 00:04:59,190 And also, there's a series of membrane compartments 86 00:04:59,190 --> 00:05:00,870 that span the cytoplasm. 87 00:05:03,570 --> 00:05:08,880 Now, our cells, even in a single organism, such as us, our cells 88 00:05:08,880 --> 00:05:15,620 have incredible diversity and specialization. 89 00:05:15,620 --> 00:05:19,220 So there's diversity within a single organism. 90 00:05:19,220 --> 00:05:21,400 There is specialization. 91 00:05:25,410 --> 00:05:30,110 So as we develop from a single cell, 92 00:05:30,110 --> 00:05:32,720 our cells acquire properties that 93 00:05:32,720 --> 00:05:38,640 allow them to carry out specific functions in our bodies. 94 00:05:38,640 --> 00:05:41,540 And an extreme example of this is shown up here. 95 00:05:41,540 --> 00:05:46,760 These are pictures or drawings of neurons from Ramon y Cajal, 96 00:05:46,760 --> 00:05:48,740 and you can see how this looks nothing 97 00:05:48,740 --> 00:05:52,640 like the cartoon picture of a cell I just showed you. 98 00:05:52,640 --> 00:05:56,030 These cells have highly dendritic sort 99 00:05:56,030 --> 00:05:58,010 of arrays of protrusions. 100 00:05:58,010 --> 00:06:01,160 And these cells have evolved such 101 00:06:01,160 --> 00:06:04,940 that they are very good at sort of transmitting information 102 00:06:04,940 --> 00:06:06,140 in the body, right? 103 00:06:06,140 --> 00:06:09,260 An extreme example of a nerve is a sciatic nerve, 104 00:06:09,260 --> 00:06:12,020 which extends from the base of your spinal cord 105 00:06:12,020 --> 00:06:13,650 all the way down into your foot. 106 00:06:13,650 --> 00:06:16,010 So it's about a meter long. 107 00:06:16,010 --> 00:06:20,120 That's an extreme specialization for a cell. 108 00:06:20,120 --> 00:06:22,490 So these cells are specialized, but what's 109 00:06:22,490 --> 00:06:28,190 important to note is that within a single organism, 110 00:06:28,190 --> 00:06:33,530 the genomic DNA of a cell is more or less the same. 111 00:06:33,530 --> 00:06:42,140 So genomic DNA is the same, with some exceptions, some of which 112 00:06:42,140 --> 00:06:43,700 we'll get to in the course. 113 00:06:43,700 --> 00:06:45,930 The genomic DNA is the same. 114 00:06:45,930 --> 00:06:47,750 What's different is the genes that 115 00:06:47,750 --> 00:06:51,740 are being expressed in these cells and the proteins 116 00:06:51,740 --> 00:06:54,680 that they encode that give these cells different functions. 117 00:06:57,260 --> 00:07:01,910 So what's different and what allows cells to acquire 118 00:07:01,910 --> 00:07:04,970 these different functionalities is this different gene 119 00:07:04,970 --> 00:07:06,085 expression. 120 00:07:21,140 --> 00:07:23,310 OK, so that's the overview. 121 00:07:23,310 --> 00:07:25,340 Now I want to talk about compartments. 122 00:07:29,100 --> 00:07:32,690 And if we go back to this cartoon 123 00:07:32,690 --> 00:07:34,612 that I showed you from your-- 124 00:07:34,612 --> 00:07:37,130 oh, I just wanted to point out that right now, 125 00:07:37,130 --> 00:07:41,180 at MIT and the Broad, there is a project 126 00:07:41,180 --> 00:07:46,490 that's ongoing to really define all the cell types that 127 00:07:46,490 --> 00:07:48,750 are present in humans. 128 00:07:48,750 --> 00:07:52,970 And this is known as the Human Cell Atlas. 129 00:07:52,970 --> 00:07:54,470 And I just want you to take a minute 130 00:07:54,470 --> 00:07:59,180 to think about if you wanted to define different cell types, 131 00:07:59,180 --> 00:08:03,110 what would you look at to classify these cell types? 132 00:08:03,110 --> 00:08:05,150 Anyone have an idea? 133 00:08:05,150 --> 00:08:05,650 Yes? 134 00:08:05,650 --> 00:08:06,160 What's your name? 135 00:08:06,160 --> 00:08:07,020 AUDIENCE: Rachel. 136 00:08:07,020 --> 00:08:07,900 ADAM MARTIN: Rachel. 137 00:08:07,900 --> 00:08:09,310 AUDIENCE: Cell function. 138 00:08:09,310 --> 00:08:09,640 ADAM MARTIN: What's that? 139 00:08:09,640 --> 00:08:10,450 AUDIENCE: Function. 140 00:08:10,450 --> 00:08:12,970 ADAM MARTIN: You could look at function. 141 00:08:12,970 --> 00:08:16,960 That might be a little subjective in how to interpret. 142 00:08:16,960 --> 00:08:19,191 What defines the function of the cell? 143 00:08:19,191 --> 00:08:20,995 AUDIENCE: I'm thinking like what it does 144 00:08:20,995 --> 00:08:22,790 and how it works with other cells. 145 00:08:22,790 --> 00:08:24,290 ADAM MARTIN: But is there something, 146 00:08:24,290 --> 00:08:25,850 I guess, within that cell that would 147 00:08:25,850 --> 00:08:29,010 define what its function is? 148 00:08:29,010 --> 00:08:29,510 Yeah? 149 00:08:29,510 --> 00:08:30,450 What's your name? 150 00:08:30,450 --> 00:08:31,213 AUDIENCE: Samantar 151 00:08:31,213 --> 00:08:32,130 ADAM MARTIN: Samantar? 152 00:08:32,130 --> 00:08:33,200 AUDIENCE: Samantar 153 00:08:33,200 --> 00:08:35,150 ADAM MARTIN: Samantac All right, yeah? 154 00:08:35,150 --> 00:08:36,530 AUDIENCE: Gene expression data. 155 00:08:36,530 --> 00:08:38,030 ADAM MARTIN: Gene expression, right? 156 00:08:38,030 --> 00:08:41,570 What genes are these cells expressing? 157 00:08:41,570 --> 00:08:45,680 So what they're doing is they're isolating single cells 158 00:08:45,680 --> 00:08:47,790 from tissues. 159 00:08:47,790 --> 00:08:49,920 And then they're looking at gene expression. 160 00:08:49,920 --> 00:08:52,820 So which type of molecule here would 161 00:08:52,820 --> 00:08:55,640 be the molecule you'd want to look at if you want 162 00:08:55,640 --> 00:08:57,172 to look at gene expression? 163 00:09:04,070 --> 00:09:05,880 Not Miles. 164 00:09:05,880 --> 00:09:07,182 Malik. 165 00:09:07,182 --> 00:09:09,265 AUDIENCE: You look at mRNA. 166 00:09:09,265 --> 00:09:10,390 ADAM MARTIN: mRNA, exactly. 167 00:09:10,390 --> 00:09:12,350 Malik is exactly right. 168 00:09:12,350 --> 00:09:14,330 So you look at the mRNA, right? 169 00:09:14,330 --> 00:09:19,550 Because if there's mRNA, that means that gene was expressed, 170 00:09:19,550 --> 00:09:24,452 and it's possibly encoding the translation of a protein. 171 00:09:24,452 --> 00:09:25,660 So that's what they're doing. 172 00:09:25,660 --> 00:09:29,450 They're isolating single cells and doing a massive single cell 173 00:09:29,450 --> 00:09:31,100 RNA seek project. 174 00:09:31,100 --> 00:09:33,140 And that's helping to identify new cell 175 00:09:33,140 --> 00:09:36,010 types in the human body. 176 00:09:36,010 --> 00:09:38,930 OK, coming back to compartments. 177 00:09:38,930 --> 00:09:40,550 So I showed you this picture. 178 00:09:40,550 --> 00:09:44,420 You can see there are lots of membrane-bound compartments 179 00:09:44,420 --> 00:09:45,040 in the cell. 180 00:09:45,040 --> 00:09:46,880 You can see the lines in this cartoon 181 00:09:46,880 --> 00:09:49,040 represent lipid bilayers. 182 00:09:49,040 --> 00:09:51,410 And so these are compartments that 183 00:09:51,410 --> 00:09:56,373 are completely encapsulated by a lipid bilayer. 184 00:09:56,373 --> 00:09:58,040 And I'm going to remind you of something 185 00:09:58,040 --> 00:10:01,100 that Professor Imperiali told you about already. 186 00:10:01,100 --> 00:10:02,720 And the reason I'm saying it again 187 00:10:02,720 --> 00:10:06,320 is because it is so freaking important, OK? 188 00:10:06,320 --> 00:10:10,670 So if we consider a lipid bilayer 189 00:10:10,670 --> 00:10:14,330 where the circles are the polar head groups of the lipids 190 00:10:14,330 --> 00:10:17,900 and the squiggly lines are the fatty acid chains-- 191 00:10:17,900 --> 00:10:20,135 I'm not going to draw all the fatty acid chains. 192 00:10:24,635 --> 00:10:25,760 So this is a lipid bilayer. 193 00:10:31,460 --> 00:10:37,810 And these head groups, are they hydrophilic or hydrophobic? 194 00:10:37,810 --> 00:10:38,310 Yes? 195 00:10:38,310 --> 00:10:38,760 What's your name? 196 00:10:38,760 --> 00:10:39,140 AUDIENCE: Stephen. 197 00:10:39,140 --> 00:10:40,184 ADAM MARTIN: Stephen. 198 00:10:40,184 --> 00:10:40,940 AUDIENCE: They're hydrophilic. 199 00:10:40,940 --> 00:10:41,880 ADAM MARTIN: They're hydrophilic. 200 00:10:41,880 --> 00:10:42,840 They like water, right? 201 00:10:42,840 --> 00:10:46,200 The water is on the different faces here. 202 00:10:46,200 --> 00:10:47,610 These are hydrophilic. 203 00:10:53,680 --> 00:10:56,570 How about this central region here? 204 00:10:56,570 --> 00:10:57,070 Yes? 205 00:10:57,070 --> 00:10:57,570 Name? 206 00:10:57,570 --> 00:10:58,240 AUDIENCE: Ory. 207 00:10:58,240 --> 00:10:59,003 ADAM MARTIN: Ory. 208 00:10:59,003 --> 00:10:59,920 AUDIENCE: Hydrophobic. 209 00:10:59,920 --> 00:11:02,620 ADAM MARTIN: Hydrophobic, good, right? 210 00:11:02,620 --> 00:11:05,230 That's excellent. 211 00:11:05,230 --> 00:11:08,910 So these are hydrophobic. 212 00:11:08,910 --> 00:11:10,360 Hydrophobic. 213 00:11:10,360 --> 00:11:14,080 So what that means is you have this hydrophobic layer that is 214 00:11:14,080 --> 00:11:16,600 surrounding each of these compartments, 215 00:11:16,600 --> 00:11:20,050 and that's going to serve as a barrier such that water 216 00:11:20,050 --> 00:11:23,050 and things dissolved in water cannot pass through this 217 00:11:23,050 --> 00:11:27,580 barrier unless something allows it to. 218 00:11:27,580 --> 00:11:30,730 So each of these compartments are membrane bound, 219 00:11:30,730 --> 00:11:34,750 have properties in the lumen that's 220 00:11:34,750 --> 00:11:36,490 in the interior of the compartment that's 221 00:11:36,490 --> 00:11:39,400 going to be different from that of the cytoplasm. 222 00:11:39,400 --> 00:11:42,310 And the cell, the interior of the cytoplasm, 223 00:11:42,310 --> 00:11:45,310 is going to be different from that of the extracellular 224 00:11:45,310 --> 00:11:47,560 space. 225 00:11:47,560 --> 00:11:49,750 So let me just give you some examples 226 00:11:49,750 --> 00:11:53,620 of how things are different inside and outside the cell 227 00:11:53,620 --> 00:11:57,320 and also inside and outside these compartments. 228 00:11:57,320 --> 00:12:07,510 So if we consider the plasma versus the cytoplasm, 229 00:12:07,510 --> 00:12:11,720 we can consider the concentration of various ions. 230 00:12:11,720 --> 00:12:14,080 And I want to get the concentrations right. 231 00:12:14,080 --> 00:12:21,430 Let's consider sodium, which is a monovalent cation, potassium, 232 00:12:21,430 --> 00:12:22,960 and calcium. 233 00:12:22,960 --> 00:12:26,290 I'm just going to use these as illustrations. 234 00:12:26,290 --> 00:12:30,190 So sodium is concentrated outside the cell, 235 00:12:30,190 --> 00:12:34,990 about 150 millimolar, and is less concentrated 236 00:12:34,990 --> 00:12:36,910 in the cytoplasm. 237 00:12:36,910 --> 00:12:41,800 So there's a huge difference in sodium between the outside 238 00:12:41,800 --> 00:12:44,740 and the inside of the cell. 239 00:12:44,740 --> 00:12:47,320 Potassium-- now, you might think potassium 240 00:12:47,320 --> 00:12:48,760 would be a lot like sodium. 241 00:12:48,760 --> 00:12:50,830 It's a monovalent cation. 242 00:12:50,830 --> 00:12:52,660 It's a similar size. 243 00:12:52,660 --> 00:12:55,350 But it actually shows the flip distribution. 244 00:12:55,350 --> 00:12:59,590 So it's four millimolar in the exoplasm 245 00:12:59,590 --> 00:13:05,350 and 140 millimolar in the cytoplasm, OK? 246 00:13:05,350 --> 00:13:08,440 So there appears to be some selectivity here, right? 247 00:13:08,440 --> 00:13:12,070 The cell is concentrating certain things 248 00:13:12,070 --> 00:13:15,850 inside the cytoplasm, and it's excluding others. 249 00:13:15,850 --> 00:13:24,010 So there's selectivity, even between closely related atoms 250 00:13:24,010 --> 00:13:25,480 here. 251 00:13:25,480 --> 00:13:31,450 OK, calcium is two millimolar in the exoplasm and around 10 252 00:13:31,450 --> 00:13:35,200 to the negative fifth millimolar in the cytoplasm. 253 00:13:38,290 --> 00:13:42,370 So because there are these huge gradients in the concentration 254 00:13:42,370 --> 00:13:45,580 of these ions leads you to expect that this 255 00:13:45,580 --> 00:13:48,040 is a non-equilibrium state. 256 00:13:48,040 --> 00:13:51,283 Because if it were equilibrium, these ions would go in and out, 257 00:13:51,283 --> 00:13:53,950 and they'd equilibrate such that the same concentration would be 258 00:13:53,950 --> 00:13:57,160 on the inside as the outside. 259 00:13:57,160 --> 00:13:58,840 And so there's selectivity. 260 00:13:58,840 --> 00:14:00,950 And also, there's non-equilibrium, 261 00:14:00,950 --> 00:14:03,880 which suggests that energy is required 262 00:14:03,880 --> 00:14:06,460 to maintain this asymmetry. 263 00:14:10,380 --> 00:14:12,890 I want to point out it's not just the concentrations 264 00:14:12,890 --> 00:14:16,010 of various molecules that are different between the inside 265 00:14:16,010 --> 00:14:19,640 and the outside, but the plasma membrane can also 266 00:14:19,640 --> 00:14:21,140 have a voltage across it. 267 00:14:25,310 --> 00:14:27,890 So this is exoplasm. 268 00:14:27,890 --> 00:14:29,060 This is cytoplasm. 269 00:14:32,580 --> 00:14:35,915 And this membrane can hold a voltage. 270 00:14:40,740 --> 00:14:43,080 And this is going to become incredibly important when 271 00:14:43,080 --> 00:14:48,870 we talk about neurons, because neurons use changes 272 00:14:48,870 --> 00:14:54,000 in this voltage to transmit signals across their length 273 00:14:54,000 --> 00:14:57,450 and also to transmit signals at the synapse. 274 00:14:57,450 --> 00:14:59,920 And we'll talk about that later in the course. 275 00:14:59,920 --> 00:15:02,540 So this is known as membrane potential, 276 00:15:02,540 --> 00:15:04,596 this voltage difference. 277 00:15:15,270 --> 00:15:20,520 I also, again, want to point out this endomembrane system 278 00:15:20,520 --> 00:15:24,150 in here, where the gray regions here 279 00:15:24,150 --> 00:15:26,400 are sort of compartments that will communicate 280 00:15:26,400 --> 00:15:28,540 with each other. 281 00:15:28,540 --> 00:15:31,050 And so there's this whole internal structure 282 00:15:31,050 --> 00:15:34,950 of endomembrane system which is compartmentalized 283 00:15:34,950 --> 00:15:38,610 from the cytoplasm, OK? 284 00:15:38,610 --> 00:15:41,130 And so now I want to talk about how do things get 285 00:15:41,130 --> 00:15:44,280 in and out of this structure. 286 00:15:44,280 --> 00:15:47,880 So I think we're up to three, getting in and out. 287 00:15:56,280 --> 00:15:59,520 So cells-- and this is very important in cell 288 00:15:59,520 --> 00:16:01,400 communication, right? 289 00:16:01,400 --> 00:16:05,160 For cells to communicate, cells have 290 00:16:05,160 --> 00:16:07,920 to send things, like signals, to other cells. 291 00:16:07,920 --> 00:16:11,220 And also, cells can take in stuff 292 00:16:11,220 --> 00:16:15,220 and sort of receive things from other cells. 293 00:16:15,220 --> 00:16:18,870 So how is it that this happens? 294 00:16:18,870 --> 00:16:22,500 Well, if we consider the plasma membrane of a cell-- 295 00:16:22,500 --> 00:16:25,080 this is a lipid bilayer, PM. 296 00:16:25,080 --> 00:16:28,410 I abbreviate Plasma Membrane, PM. 297 00:16:28,410 --> 00:16:30,200 So that's a lipid bilayer. 298 00:16:30,200 --> 00:16:37,320 And let's say that there's some type of sort of molecule 299 00:16:37,320 --> 00:16:39,700 that's on the outside of the cell. 300 00:16:39,700 --> 00:16:44,400 So, in this case, this would be exoplasm out here. 301 00:16:44,400 --> 00:16:48,930 This would be inside the cytoplasm here. 302 00:16:48,930 --> 00:16:51,900 Let's say this cell wanted to sort of take up 303 00:16:51,900 --> 00:16:57,810 this pink structure into the cell. 304 00:16:57,810 --> 00:16:59,380 How would it do that? 305 00:16:59,380 --> 00:17:02,670 Well, this pink structure, because it's hydrophilic, 306 00:17:02,670 --> 00:17:06,990 cannot pass through the lipid bilayer. 307 00:17:06,990 --> 00:17:09,390 So the cell has to use another strategy 308 00:17:09,390 --> 00:17:11,109 to take this up into the cell. 309 00:17:17,089 --> 00:17:17,760 Let's see. 310 00:17:17,760 --> 00:17:19,540 I'll use a little blue here. 311 00:17:19,540 --> 00:17:23,319 So let's say the region of the membrane right here is in blue. 312 00:17:23,319 --> 00:17:31,850 Then, what can happen is this blue structure can invaginate, 313 00:17:31,850 --> 00:17:34,370 and it can take up this pink molecule. 314 00:17:37,160 --> 00:17:41,360 So the plasma membrane can invaginate. 315 00:17:41,360 --> 00:17:44,030 The plasma membrane can invaginate, 316 00:17:44,030 --> 00:17:46,700 and if it has this pink molecule, 317 00:17:46,700 --> 00:17:50,960 then if there is a cision event here, 318 00:17:50,960 --> 00:17:54,260 you've now gone from having your pink molecule 319 00:17:54,260 --> 00:17:56,390 on the outside of the cell to having 320 00:17:56,390 --> 00:18:02,090 the pink molecule in this vesicle or circular structure 321 00:18:02,090 --> 00:18:04,640 on the inside of the cell. 322 00:18:04,640 --> 00:18:07,880 So here now we have this. 323 00:18:07,880 --> 00:18:10,730 We have our vesicle in blue. 324 00:18:10,730 --> 00:18:15,140 And now the cell has picked up this pink molecule, 325 00:18:15,140 --> 00:18:17,900 such like this. 326 00:18:17,900 --> 00:18:22,940 So this process of sort of taking material 327 00:18:22,940 --> 00:18:25,010 from the outside and sort of bringing it 328 00:18:25,010 --> 00:18:27,500 into the inside of the cell is known 329 00:18:27,500 --> 00:18:38,180 as endocytosis, which is the process of taking something 330 00:18:38,180 --> 00:18:42,770 from the outside and bringing it in the cell, this is also 331 00:18:42,770 --> 00:18:44,840 a way that viruses can get in your cells, 332 00:18:44,840 --> 00:18:49,010 which is a more nefarious way that this system is used. 333 00:18:49,010 --> 00:18:51,530 All right, I need a volunteer. 334 00:18:51,530 --> 00:18:52,740 Yes. 335 00:18:52,740 --> 00:18:54,290 Ory, come on down. 336 00:18:59,510 --> 00:19:01,490 Don't worry. 337 00:19:01,490 --> 00:19:03,120 This'll be simple. 338 00:19:03,120 --> 00:19:06,740 I just need you to put pressure on my head right here. 339 00:19:06,740 --> 00:19:07,940 So you see the tassel. 340 00:19:07,940 --> 00:19:09,740 Make sure they can see the tassel. 341 00:19:09,740 --> 00:19:11,130 You see this tassel? 342 00:19:11,130 --> 00:19:13,220 This tassel is that pink molecule, 343 00:19:13,220 --> 00:19:16,640 is right now on the outside, right? 344 00:19:16,640 --> 00:19:19,750 But I'm going to endocytose it by going like that, right? 345 00:19:19,750 --> 00:19:20,990 And I also got a hand. 346 00:19:20,990 --> 00:19:22,250 That's great. 347 00:19:22,250 --> 00:19:25,670 So you see, that's basically endocytosis. 348 00:19:25,670 --> 00:19:29,630 I just endocytosed my tassel. 349 00:19:29,630 --> 00:19:30,980 All right, you can go up. 350 00:19:30,980 --> 00:19:32,420 We're all set, yeah. 351 00:19:32,420 --> 00:19:35,690 I can do the next one. 352 00:19:35,690 --> 00:19:38,630 OK, so the opposite of this process-- 353 00:19:38,630 --> 00:19:39,880 let me get another color here. 354 00:19:44,360 --> 00:19:47,930 You can also have vesicles that are on the inside that then 355 00:19:47,930 --> 00:19:51,590 fuse with the plasma membrane and release their contents 356 00:19:51,590 --> 00:19:52,280 to the exterior. 357 00:19:56,360 --> 00:19:58,710 And this is called exocytosis. 358 00:20:02,900 --> 00:20:05,930 So exocytosis is something that's 359 00:20:05,930 --> 00:20:11,690 starting out inside one of these vesicles and then goes out, OK? 360 00:20:11,690 --> 00:20:13,850 So this is not exactly reversible, 361 00:20:13,850 --> 00:20:16,400 because there are different protein machineries that 362 00:20:16,400 --> 00:20:20,060 mediate either endocytosis or exocytosis. 363 00:20:20,060 --> 00:20:22,385 So now I'm going to exocytose my tassel. 364 00:20:24,920 --> 00:20:25,730 There we go. 365 00:20:25,730 --> 00:20:29,210 So I just exocytosed it, and now my molecules is again 366 00:20:29,210 --> 00:20:32,930 facing the outside world. 367 00:20:32,930 --> 00:20:36,320 So this is a way for cells to sort of taken things 368 00:20:36,320 --> 00:20:41,630 and also to secrete molecules, like signaling molecules, 369 00:20:41,630 --> 00:20:43,430 into the extracellular space. 370 00:20:47,220 --> 00:20:50,090 So now, we're moving on, and now we're 371 00:20:50,090 --> 00:20:54,980 going to talk about compartments within compartments. 372 00:20:54,980 --> 00:20:57,050 So we're on four-- 373 00:20:57,050 --> 00:21:04,370 compartments within compartments. 374 00:21:04,370 --> 00:21:07,550 And you're going to see how this relates to endocytosis 375 00:21:07,550 --> 00:21:08,400 in just a minute. 376 00:21:11,670 --> 00:21:16,100 So compartments within compartments. 377 00:21:16,100 --> 00:21:18,350 So the example I'm going to use here 378 00:21:18,350 --> 00:21:21,020 is an organelle that is present in us, 379 00:21:21,020 --> 00:21:23,690 in animal cells, which is the mitochondria. 380 00:21:31,970 --> 00:21:35,240 And you all know that the mitochondria 381 00:21:35,240 --> 00:21:39,530 is the powerhouse of the cell. 382 00:21:39,530 --> 00:21:42,230 Whenever I say mitochondria is the powerhouse of the cells, 383 00:21:42,230 --> 00:21:46,155 I have to do 10 push-ups, because it's so cliche. 384 00:21:52,580 --> 00:21:54,800 I mean, my five-year-old knows that mitochondria 385 00:21:54,800 --> 00:21:56,580 is the powerhouse of the cell. 386 00:21:56,580 --> 00:22:00,200 It's a gross oversimplification, OK? 387 00:22:00,200 --> 00:22:02,810 Mitochondria are way more interesting than that, 388 00:22:02,810 --> 00:22:05,630 and I'll show you in just a minute. 389 00:22:05,630 --> 00:22:10,160 All right, I'll draw mitochondria, 390 00:22:10,160 --> 00:22:13,910 the same mitochondria that my kids draw me. 391 00:22:13,910 --> 00:22:16,220 So here's a mitochondria. 392 00:22:16,220 --> 00:22:18,950 I'm drawing first the outer membrane. 393 00:22:24,430 --> 00:22:27,430 So there's an outer membrane to the mitochondria. 394 00:22:27,430 --> 00:22:29,785 And this organelle also has an inner membrane. 395 00:22:34,145 --> 00:22:35,395 So this is the inner membrane. 396 00:22:43,970 --> 00:22:46,735 The inside here is called the matrix. 397 00:22:49,990 --> 00:22:54,220 I'll draw some DNA molecules there. 398 00:22:54,220 --> 00:22:59,650 So this is known as the mitochondrial DNA, which 399 00:22:59,650 --> 00:23:00,910 I'll mention in just a minute. 400 00:23:05,970 --> 00:23:08,550 So this is the mitochondria. 401 00:23:08,550 --> 00:23:12,420 Where could such an organelle come from, evolutionarily 402 00:23:12,420 --> 00:23:14,330 speaking? 403 00:23:14,330 --> 00:23:18,090 You know, one problem that eukaryotic cells have is they 404 00:23:18,090 --> 00:23:21,390 cannot make mitochondria de novo. 405 00:23:21,390 --> 00:23:24,360 The way that mitochondria is passed on 406 00:23:24,360 --> 00:23:27,240 is it's replicated during cell division, 407 00:23:27,240 --> 00:23:30,540 and it's passed on from one cell to the next. 408 00:23:30,540 --> 00:23:33,420 And you guys all got your mitochondrial DNA 409 00:23:33,420 --> 00:23:38,220 and your mitochondria, at least initially, from your mother. 410 00:23:38,220 --> 00:23:42,180 So this is not an organelle that can be synthesized de novo. 411 00:23:42,180 --> 00:23:44,220 And the fact that this is the case 412 00:23:44,220 --> 00:23:48,030 has led to a theory known as the endosymbiont theory, 413 00:23:48,030 --> 00:23:52,830 or hypothesis, which basically states that there was 414 00:23:52,830 --> 00:23:55,650 an ancestral eukaryotic cell. 415 00:23:55,650 --> 00:23:59,490 And the way that organelles such as mitochondria and plastids 416 00:23:59,490 --> 00:24:04,770 were derived is from engulfing bacterial cells that 417 00:24:04,770 --> 00:24:07,440 were either capable of oxidative phosphorylation, 418 00:24:07,440 --> 00:24:13,200 in the case of mitochondria, or were capable of photosynthesis, 419 00:24:13,200 --> 00:24:17,090 in the case of chloroplasts. 420 00:24:17,090 --> 00:24:21,630 And so this engulfment is much like this endocytic process 421 00:24:21,630 --> 00:24:22,980 that I just talked to you. 422 00:24:22,980 --> 00:24:25,710 It's not really endocytosis, because these bacteria 423 00:24:25,710 --> 00:24:28,590 are much better than an endocytic vesicle. 424 00:24:28,590 --> 00:24:34,800 So it's more of like a macro sort of pinocytosis 425 00:24:34,800 --> 00:24:36,480 or something like that, OK? 426 00:24:40,470 --> 00:24:45,600 So something you may have seen in the news lately-- 427 00:24:45,600 --> 00:24:50,280 so some of the evidence for this endosymbiont theory 428 00:24:50,280 --> 00:24:54,240 is that mitochondria and plastids have their own DNA, 429 00:24:54,240 --> 00:24:56,520 OK? 430 00:24:56,520 --> 00:24:59,310 So these organelles have retained DNA. 431 00:25:06,660 --> 00:25:10,110 The genes in the DNA encode for proteins, that 432 00:25:10,110 --> 00:25:12,280 function in the mitochondria. 433 00:25:12,280 --> 00:25:16,630 It also includes ribosomal RNAs and transfer RNAs 434 00:25:16,630 --> 00:25:19,110 that are required for protein synthesis 435 00:25:19,110 --> 00:25:21,270 within the mitochondria. 436 00:25:21,270 --> 00:25:24,390 But a lot of the genes that are required for a functioning 437 00:25:24,390 --> 00:25:28,440 organism have now been exported to our nuclear DNA, 438 00:25:28,440 --> 00:25:30,630 and those genes are made and proteins are produced, 439 00:25:30,630 --> 00:25:33,120 and then they're imported into the mitochondria. 440 00:25:33,120 --> 00:25:37,620 But the mitochondria has retained a number of genes, 441 00:25:37,620 --> 00:25:41,490 and it's encoded in the mitochondrial DNA. 442 00:25:41,490 --> 00:25:43,050 Another reason to think that this 443 00:25:43,050 --> 00:25:46,500 could be from a symbiotic relationship, this ancient, 444 00:25:46,500 --> 00:25:49,410 between eukaryotic and prokaryotic cells 445 00:25:49,410 --> 00:25:53,070 is that these organelles divide by fission 446 00:25:53,070 --> 00:25:56,700 similar to how bacteria divide. 447 00:25:56,700 --> 00:25:58,110 So they divide by fission. 448 00:26:06,020 --> 00:26:08,270 So I'll show you a real mitochondria 449 00:26:08,270 --> 00:26:11,420 and a mitochondria undergoing fission in just a minute. 450 00:26:11,420 --> 00:26:15,950 I just want to point out that in the news recently, 451 00:26:15,950 --> 00:26:20,480 there's been talk of three-parent babies. 452 00:26:20,480 --> 00:26:24,300 And I just want to explain to you what that is. 453 00:26:24,300 --> 00:26:27,590 So eggs that are-- 454 00:26:27,590 --> 00:26:31,580 I shouldn't say embryos, but eggs 455 00:26:31,580 --> 00:26:35,360 that have the nuclear DNA from two parents 456 00:26:35,360 --> 00:26:39,380 can then be given mitochondrial DNA from another parent. 457 00:26:39,380 --> 00:26:41,900 So these three-parent babies are essentially 458 00:26:41,900 --> 00:26:45,350 babies that have nuclear DNA from two 459 00:26:45,350 --> 00:26:50,900 parents but mitochondrial DNA from a third parent. 460 00:26:50,900 --> 00:26:55,010 So here's just an article in the NewScientist reporting 461 00:26:55,010 --> 00:26:59,450 that this is imminent, and now it's been done. 462 00:26:59,450 --> 00:27:01,520 Now, why would you might want to do that? 463 00:27:01,520 --> 00:27:03,920 Anyone know why someone would want to do this? 464 00:27:07,470 --> 00:27:08,296 Yes? 465 00:27:08,296 --> 00:27:10,713 AUDIENCE: There might be a defect in the mitochondrial DNA 466 00:27:10,713 --> 00:27:11,950 of both parents. 467 00:27:11,950 --> 00:27:12,700 ADAM MARTIN: Yeah. 468 00:27:12,700 --> 00:27:13,747 So Stephen, right? 469 00:27:13,747 --> 00:27:14,330 AUDIENCE: Yes. 470 00:27:14,330 --> 00:27:16,560 ADAM MARTIN: Stephen's exactly right, right? 471 00:27:16,560 --> 00:27:19,020 There are diseases that are so associated 472 00:27:19,020 --> 00:27:22,150 with faulty mitochondrial DNA. 473 00:27:22,150 --> 00:27:26,970 And if you're a mother and you have the mutations that 474 00:27:26,970 --> 00:27:30,510 cause this disease, this would be a way for you 475 00:27:30,510 --> 00:27:35,550 to have a child without passing on the disease to your child. 476 00:27:35,550 --> 00:27:39,690 And so this is something that is still controversial, 477 00:27:39,690 --> 00:27:43,680 but that's why people are exploring the opportunity 478 00:27:43,680 --> 00:27:48,460 for making these so-called three-parent babies. 479 00:27:48,460 --> 00:27:51,120 Again, I've a pet peeve with textbook pictures 480 00:27:51,120 --> 00:27:52,590 of mitochondria. 481 00:27:52,590 --> 00:27:54,150 Here's your textbook picture. 482 00:27:54,150 --> 00:27:55,950 Everything's labeled nicely. 483 00:27:55,950 --> 00:27:59,220 This is what mitochondria look like in real life. 484 00:27:59,220 --> 00:28:02,670 Mitochondria, like the endoplasmic reticulum, 485 00:28:02,670 --> 00:28:06,360 actually, form these tubular networks that essentially 486 00:28:06,360 --> 00:28:08,790 span the entire cell. 487 00:28:08,790 --> 00:28:11,460 So it's convenient for us to depict mitochondria 488 00:28:11,460 --> 00:28:14,430 like this in textbook, but mitochondria are 489 00:28:14,430 --> 00:28:16,140 way more interesting than that. 490 00:28:16,140 --> 00:28:18,240 They're dynamic organelles. 491 00:28:18,240 --> 00:28:21,030 And I also want to make the point-- we kind of talk 492 00:28:21,030 --> 00:28:23,040 about these organelles like they behave 493 00:28:23,040 --> 00:28:25,980 as these separate entities, but in fact, they 494 00:28:25,980 --> 00:28:27,250 interact with each other. 495 00:28:27,250 --> 00:28:30,810 And there's lots of interesting biology behind that. 496 00:28:30,810 --> 00:28:33,210 So I'm going to show you one movie that's 497 00:28:33,210 --> 00:28:37,350 from work done by Gia Voeltz, and this Friedman person 498 00:28:37,350 --> 00:28:38,920 is the first author. 499 00:28:38,920 --> 00:28:41,100 She just gave a talk here at MIT and showed 500 00:28:41,100 --> 00:28:43,030 some beautiful movies. 501 00:28:43,030 --> 00:28:44,970 All right, focus on this movie here. 502 00:28:44,970 --> 00:28:49,350 The ER is labeled in green, and the mitochondria is in red. 503 00:28:49,350 --> 00:28:52,040 And what you see is there is this mitochondria tubule, 504 00:28:52,040 --> 00:28:55,500 and it's crossed by the ER right here. 505 00:28:55,500 --> 00:28:58,680 Now, focus on this when the movie plays. 506 00:28:58,680 --> 00:29:01,680 You're going to see that the mitochondria undergoes fission 507 00:29:01,680 --> 00:29:04,830 right at these points, where the ER and the mitochondria 508 00:29:04,830 --> 00:29:06,570 intersect. 509 00:29:06,570 --> 00:29:09,660 So that illustrates-- and now they've mechanistically 510 00:29:09,660 --> 00:29:13,350 dissected what sort of makes the mitochondria undergo fission 511 00:29:13,350 --> 00:29:15,360 at these crossing sites. 512 00:29:15,360 --> 00:29:17,700 But it really illustrates the real sort 513 00:29:17,700 --> 00:29:20,340 of complexity and dynamics that are 514 00:29:20,340 --> 00:29:22,770 present in a cell, which you might not 515 00:29:22,770 --> 00:29:25,170 be getting from your book. 516 00:29:25,170 --> 00:29:28,020 Oh, I did want to mention that-- 517 00:29:28,020 --> 00:29:30,330 so there's a chapter in your book-- 518 00:29:30,330 --> 00:29:33,030 I think it's Key Concept 5.3-- 519 00:29:33,030 --> 00:29:36,090 where you can read about all the organelles. 520 00:29:36,090 --> 00:29:40,560 You should read that and know roughly what the organelles do. 521 00:29:40,560 --> 00:29:42,420 I mean, I could lecture about that, 522 00:29:42,420 --> 00:29:46,470 but it would just be so boring that I can't do it. 523 00:29:46,470 --> 00:29:49,290 I'd have to do a ton of push-ups. 524 00:29:49,290 --> 00:29:55,150 So we have to sort of choose what we lecture about. 525 00:29:55,150 --> 00:29:58,170 So I would just suggest you read that part in the textbook. 526 00:29:58,170 --> 00:30:01,500 If you have questions, come talk to me. 527 00:30:01,500 --> 00:30:04,370 And just be familiar with what your organelles are doing. 528 00:30:04,370 --> 00:30:04,888 Yes, Ory? 529 00:30:04,888 --> 00:30:06,180 AUDIENCE: What was the chapter? 530 00:30:06,180 --> 00:30:08,535 ADAM MARTIN: It's 5.3. 531 00:30:08,535 --> 00:30:09,900 AUDIENCE: Is it like a chapter? 532 00:30:09,900 --> 00:30:12,210 ADAM MARTIN: It's Key Concept 5.3. 533 00:30:12,210 --> 00:30:14,453 It's probably listed in the assignments, right? 534 00:30:14,453 --> 00:30:16,120 AUDIENCE: It's a section in the chapter. 535 00:30:16,120 --> 00:30:16,870 ADAM MARTIN: Yeah. 536 00:30:16,870 --> 00:30:18,837 AUDIENCE: It's only a little bit. 537 00:30:18,837 --> 00:30:20,298 It's not going to be long. 538 00:30:24,690 --> 00:30:25,810 ADAM MARTIN: All right. 539 00:30:25,810 --> 00:30:29,080 I have one last part, which is to prepare you 540 00:30:29,080 --> 00:30:31,210 for Friday's lecture. 541 00:30:31,210 --> 00:30:32,920 In Friday's lecture, we're going to start 542 00:30:32,920 --> 00:30:34,750 talking about genetics. 543 00:30:34,750 --> 00:30:36,370 And before we talk about genetics, 544 00:30:36,370 --> 00:30:38,740 we're going to talk about something that is-- 545 00:30:38,740 --> 00:30:40,870 we're going to lay the groundwork, essentially, 546 00:30:40,870 --> 00:30:44,050 for genetics by talking about how cells divide. 547 00:30:44,050 --> 00:30:46,750 So I think one of the most miraculous things 548 00:30:46,750 --> 00:30:51,400 that cells do is that they can undergo this trick where 549 00:30:51,400 --> 00:30:54,640 they replicate themselves and split it into two daughter 550 00:30:54,640 --> 00:30:55,250 cells. 551 00:30:55,250 --> 00:30:58,090 And you're seeing here, there are chromosomes in the middle 552 00:30:58,090 --> 00:30:58,870 here. 553 00:30:58,870 --> 00:31:02,030 They're going to line up along the metaphase plate. 554 00:31:02,030 --> 00:31:04,790 And now they're going to get pulled to separate sides. 555 00:31:04,790 --> 00:31:07,030 They're going to wiggle back and forth first. 556 00:31:09,740 --> 00:31:12,350 Then, in just a minute, they're going to get segregated. 557 00:31:12,350 --> 00:31:13,761 They'll go eventually. 558 00:31:17,530 --> 00:31:19,690 There they go. 559 00:31:19,690 --> 00:31:21,550 So you see-- and then the cell is 560 00:31:21,550 --> 00:31:25,360 going to pinch at the equator and divide in two, OK? 561 00:31:25,360 --> 00:31:27,850 So now I'm at this last part, the cytoskeleton, 562 00:31:27,850 --> 00:31:32,260 because the cytoskeleton is the answer to part 563 00:31:32,260 --> 00:31:36,490 of how these cells divide. 564 00:31:36,490 --> 00:31:39,580 And before I present the cytoskeleton, 565 00:31:39,580 --> 00:31:42,070 I just want to briefly mention chromosomes 566 00:31:42,070 --> 00:31:43,730 and what they look like. 567 00:31:43,730 --> 00:31:46,360 So the chromosomes are your nuclear DNA. 568 00:31:46,360 --> 00:31:49,600 They're linear pieces of DNA, as opposed to the mitochondria, 569 00:31:49,600 --> 00:31:51,830 which has circular DNA. 570 00:31:51,830 --> 00:31:54,700 And again, the fact that mitochondria have circular DNA 571 00:31:54,700 --> 00:31:58,630 is analogous with sort of bacterial chromosomes, where 572 00:31:58,630 --> 00:32:02,350 bacteria have circular DNA. 573 00:32:02,350 --> 00:32:06,190 But our chromosomes are linear pieces of DNA. 574 00:32:06,190 --> 00:32:09,160 And you guys have probably all seen chromosome spreads 575 00:32:09,160 --> 00:32:12,620 that look like this. 576 00:32:12,620 --> 00:32:17,440 So this would be a chromosome that's replicated. 577 00:32:17,440 --> 00:32:19,870 There are two copies, one and two. 578 00:32:19,870 --> 00:32:27,310 So this is a replicated and condensed chromosome, right? 579 00:32:27,310 --> 00:32:30,010 Initially, chromosomes are just like bowls of spaghetti. 580 00:32:30,010 --> 00:32:31,690 Everything's mixed together. 581 00:32:31,690 --> 00:32:35,290 But during mitosis, the chromosomes condense, and then 582 00:32:35,290 --> 00:32:38,260 they sort of resolve from each other, such 583 00:32:38,260 --> 00:32:40,840 that you can see the arms of the chromosome. 584 00:32:40,840 --> 00:32:43,630 And you can see where the chromosomes are coupled 585 00:32:43,630 --> 00:32:45,980 to each other at this structure here, 586 00:32:45,980 --> 00:32:47,867 which is known as the centromere. 587 00:32:52,180 --> 00:32:55,870 And at this centromere, a protein complex assembles. 588 00:32:59,380 --> 00:33:01,720 I'll just draw it like this. 589 00:33:01,720 --> 00:33:04,489 This protein complex is called the kinetochore. 590 00:33:08,710 --> 00:33:11,140 The kinetochore is a complex of hundreds 591 00:33:11,140 --> 00:33:15,730 of proteins that assemble into this large platform that 592 00:33:15,730 --> 00:33:17,800 sits on the centromere. 593 00:33:17,800 --> 00:33:20,650 And the kinetochore is able to attach 594 00:33:20,650 --> 00:33:24,880 to the cell's cytoskeleton, specifically microtubules. 595 00:33:24,880 --> 00:33:30,400 So this attaches to microtubules. 596 00:33:30,400 --> 00:33:34,300 And I will tell you what microtubules are right now. 597 00:33:34,300 --> 00:33:39,220 So microtubules are a component of the cell's cytoskeleton. 598 00:33:44,600 --> 00:33:48,970 So the cell's cytoskeleton is a network of filamentous rods 599 00:33:48,970 --> 00:33:50,950 that are present in the cell. 600 00:33:50,950 --> 00:33:52,870 And the term cytoskeleton kind of 601 00:33:52,870 --> 00:33:55,360 makes it sound boring, I think, because it 602 00:33:55,360 --> 00:33:56,890 makes it sound static. 603 00:33:56,890 --> 00:34:00,100 But the cytoskeleton is anything but static. 604 00:34:00,100 --> 00:34:03,500 It's actually a dynamic machine in the cell. 605 00:34:03,500 --> 00:34:07,210 And these machines that are assembled from these fibers 606 00:34:07,210 --> 00:34:08,514 are able to generate force. 607 00:34:11,170 --> 00:34:14,889 So these microtubules and the cytoskeleton, 608 00:34:14,889 --> 00:34:18,400 they generate force. 609 00:34:18,400 --> 00:34:23,050 You can think of them as motors or machines. 610 00:34:23,050 --> 00:34:24,954 So there are machines that generate force. 611 00:34:27,469 --> 00:34:31,000 And I'll just illustrate this with a couple of videos 612 00:34:31,000 --> 00:34:33,170 and slides. 613 00:34:33,170 --> 00:34:38,260 So, again, this is not a stable structure, but very dynamic. 614 00:34:38,260 --> 00:34:41,710 So this is going to be a movie where, in green here, 615 00:34:41,710 --> 00:34:46,280 microtubules are labeled, and the red label's the nucleus. 616 00:34:46,280 --> 00:34:49,389 And these cells in this fly embryo 617 00:34:49,389 --> 00:34:53,332 are going to undergo cycles of nuclear division. 618 00:34:53,332 --> 00:34:55,540 And so you're going to see the microtubules assemble, 619 00:34:55,540 --> 00:34:59,080 disassemble, assemble, disassemble. 620 00:34:59,080 --> 00:35:01,870 So you see how dynamic this process is. 621 00:35:01,870 --> 00:35:04,720 The cell is able to assemble this force-generating 622 00:35:04,720 --> 00:35:08,470 apparatus, which is known as the mitotic spindle, each 623 00:35:08,470 --> 00:35:10,390 and every cell division. 624 00:35:10,390 --> 00:35:12,910 So this structure, or machine, is 625 00:35:12,910 --> 00:35:16,180 critical to physically segregate the chromosomes 626 00:35:16,180 --> 00:35:17,920 to opposite poles of a cell. 627 00:35:22,180 --> 00:35:24,640 So now I'm going to tell you about the microtubules 628 00:35:24,640 --> 00:35:27,790 themselves. 629 00:35:27,790 --> 00:35:36,050 So microtubules, as the name implies, 630 00:35:36,050 --> 00:35:39,250 are sort of tube-like polymers. 631 00:35:39,250 --> 00:35:45,340 So these microtubules are biopolymers, 632 00:35:45,340 --> 00:35:49,480 which means that cells are expressing sort of genes that 633 00:35:49,480 --> 00:35:53,140 encode for proteins that form a subunit that can then 634 00:35:53,140 --> 00:35:57,440 self-assemble into a larger rod-like structure. 635 00:35:57,440 --> 00:36:01,070 And you can see one of these rod-like structures here. 636 00:36:01,070 --> 00:36:03,580 They essentially look like straws. 637 00:36:03,580 --> 00:36:07,510 They're about 25 nanometers in diameter. 638 00:36:07,510 --> 00:36:09,940 And I'm going to show you this video showing 639 00:36:09,940 --> 00:36:12,520 you microtubules both disassembling at first 640 00:36:12,520 --> 00:36:13,900 and then assembling. 641 00:36:13,900 --> 00:36:16,330 So that's a dissembling microtubule. 642 00:36:16,330 --> 00:36:19,420 But they also assemble to form these longer 643 00:36:19,420 --> 00:36:23,200 rod-like structures. 644 00:36:23,200 --> 00:36:29,310 So these biopolymers are dynamic, 645 00:36:29,310 --> 00:36:34,540 and they both assemble but also disassemble. 646 00:36:34,540 --> 00:36:40,430 And both the assembly and the disassembly can generate force. 647 00:36:40,430 --> 00:36:43,900 Microtubules can push if they polymerize into something. 648 00:36:43,900 --> 00:36:45,010 They push it, right? 649 00:36:45,010 --> 00:36:50,030 Just like you're kind of poking someone with your finger. 650 00:36:50,030 --> 00:36:52,660 Now, they also disassemble, and when 651 00:36:52,660 --> 00:36:56,690 they shrink and disassemble, they can actually pull. 652 00:36:56,690 --> 00:37:00,590 And I'll show you an example of that right here. 653 00:37:00,590 --> 00:37:04,030 So this is an example that's reconstituted, meaning they're 654 00:37:04,030 --> 00:37:05,590 just purified proteins here. 655 00:37:05,590 --> 00:37:07,830 There's no cell. 656 00:37:07,830 --> 00:37:10,720 And what this is, is a bead. 657 00:37:10,720 --> 00:37:14,890 And you see the dark stripe here is a microtubule. 658 00:37:14,890 --> 00:37:16,010 You can see it growing. 659 00:37:16,010 --> 00:37:17,770 There's the end right there. 660 00:37:17,770 --> 00:37:20,510 That microtubule's going to grow. 661 00:37:20,510 --> 00:37:22,670 It's going to grow out to about here. 662 00:37:22,670 --> 00:37:24,638 And then at the end of the movie, 663 00:37:24,638 --> 00:37:26,680 it's going to stop growing, and the microtubule's 664 00:37:26,680 --> 00:37:27,755 going to shrink back. 665 00:37:27,755 --> 00:37:30,130 And you're going to see that when the microtubule shrinks 666 00:37:30,130 --> 00:37:33,430 back, it's going to actually pull this large bead 667 00:37:33,430 --> 00:37:37,518 and pull it towards the left side of the slide. 668 00:37:37,518 --> 00:37:38,060 Here it goes. 669 00:37:38,060 --> 00:37:39,670 It depolymerizes and pulls. 670 00:37:39,670 --> 00:37:41,170 You see it? 671 00:37:41,170 --> 00:37:44,170 So these microtubules can generate 672 00:37:44,170 --> 00:37:48,400 a pulling force that's strong enough to pull this glass bead. 673 00:37:48,400 --> 00:37:54,070 And also, it's strong enough to pull an entire chromosome. 674 00:37:54,070 --> 00:37:56,160 It's actually much stronger-- 675 00:37:56,160 --> 00:37:58,180 it generates much more force than it 676 00:37:58,180 --> 00:38:01,030 requires to pull a chromosome. 677 00:38:01,030 --> 00:38:04,060 So it seems like there's some robustness in the system 678 00:38:04,060 --> 00:38:05,680 so that it's generating a pull that's 679 00:38:05,680 --> 00:38:08,800 much stronger than needed to actually drag a chromosome 680 00:38:08,800 --> 00:38:12,370 through viscus media. 681 00:38:12,370 --> 00:38:15,550 So during mitosis, the way this system is set up 682 00:38:15,550 --> 00:38:18,940 is there's what's known as a bipolar spindle. 683 00:38:18,940 --> 00:38:20,140 I'll just write down that. 684 00:38:20,140 --> 00:38:23,260 We'll come back to it in Friday's lecture. 685 00:38:23,260 --> 00:38:24,595 There's a bipolar spindle. 686 00:38:28,620 --> 00:38:34,810 And the bipolar spindle is made up of a number of microtubules. 687 00:38:34,810 --> 00:38:39,550 So here, you can see there are two poles, here and here. 688 00:38:39,550 --> 00:38:43,300 And in the middle, along the sort of equator of the cell, 689 00:38:43,300 --> 00:38:44,980 the chromosomes will line up. 690 00:38:44,980 --> 00:38:47,230 There are just two chromosomes here. 691 00:38:47,230 --> 00:38:50,770 And you can see how microtubules reach out from the pole 692 00:38:50,770 --> 00:38:54,190 and attach to both sides of that chromosome. 693 00:38:54,190 --> 00:38:58,390 And you can imagine that when these microtubules are 694 00:38:58,390 --> 00:39:01,240 told to shrink and disassemble, if they're 695 00:39:01,240 --> 00:39:04,955 able to remain attached to that kinetochore, which they are, 696 00:39:04,955 --> 00:39:06,580 when they shrink, they're going to pull 697 00:39:06,580 --> 00:39:11,270 the two copies of the chromosome away from each other, OK? 698 00:39:11,270 --> 00:39:13,870 And so this is the basic machinery 699 00:39:13,870 --> 00:39:17,650 that allows for chromosomes to be segregated in cells. 700 00:39:20,340 --> 00:39:22,700 OK, that's it for today. 701 00:39:22,700 --> 00:39:25,340 Any questions? 702 00:39:25,340 --> 00:39:26,300 All right, terrific. 703 00:39:26,300 --> 00:39:28,130 Good luck on your exam on Wednesday. 704 00:39:28,130 --> 00:39:29,980 It's in here.