Hey guys, today we're going to be talking about chapter 9, which covers the cell cycle. So basically, what are the key roles for cellular division? So cellular division describes an organism's ability to produce more of their own kind, and it distinguishes our living things from our non-living things.
So our biotic things from our abiotic things. Okay, it's actually characteristic of life to be able to replicate or to reproduce. So cell division is one way that we can do this. So for humans, we are multicellular, and this is a way that we can grow and repair our bodies. But if you are a unicellular organism, this is how you would reproduce.
This is how you'd make more of your own kind. So the continuity of life is based on the reproduction of cells, and that whole process is accomplished by something called cellular division. Now, I do want to point out to you that cellular division is just one part of the process. part of our overall cell cycle, which is what we're going to be focusing on today.
So cell division is actually the second part of that, whereas obviously the first part would be the cells growing and doing their daily functions. So here's an image, it's a really cool little rainbow gradient for you, that shows you that we start off with one cell, it's kind of following the chromosomes here. You start off with one cell, you can see that the nuclear envelope dissolves, you have the condensation of all of the chromosomes. Chromosomes kind of line up, they split apart, you eventually end up with two cells that very closely resemble the first one because they are genetically identical copies of it. All right, so unicellular organisms utilize cellular division.
So from one cell to reproduce the entire organism. So we have some very, very small organisms like an amoeba that actually are only one cell large, they're unicellular. So when they go through cellular division, they're actually just...
replicating themselves and that's reproduction. It's a method of asexual reproduction. Cell division actually allows us as multicellular eukaryotes to develop from a single cell. That single cell is called the zygote. Remember that a sperm cell and an egg cell will come together to form a zygote and that's the first single cell that created you.
And then once fully grown, you can use cellular division to renew your tissues, to repair your body, replace cells that are needed or because they're damaged or injured or whatever, right? So cellular division is a huge integral part of the cell cycle, which is what I was referring to earlier. It's not the whole cell cycle, the whole cell's life, but it is, you know, an important process that our cells do to help keep us growing and, you know, alive all the time. And this is, of course, like I said, something that is a characteristic of life. So living things do this, whereas non-living things do not.
So here's an image of a... A is reproduction. So this is an amoeboid little creature here. So a little amoeba that's actually undergoing asexual reproduction. So it's making a copy of itself through cellular division.
Because it's one cell, when you make a copy of it, you now have two whole organisms. And B and C are showing you growth and repair. So this is something that we would utilize because, you know, we're not growing from a single cell anymore.
You know, you are growing and repairing your body now. But it's through a very similar process. cellular division.
All right, so we're going to start off by talking about how cellular division results in genetically identical daughter cells. And this is something really important. Okay, most cells, most cellular division results in the distribution of genetical, genetical, I can speak today, identical genetic material or DNA into two daughter cells. Okay, DNA is going to be passed from one generation of cells to the next generation of cells.
So essentially you have one cell that you are trying to replicate. So you are going to split that cell into two cells. So your two resulting cells down at the bottom are going to be genetically identical to each other. And that's kind of what this whole process is talking about. So it's going to be genetically identical to the first one and to each other.
Okay, so cellular organization of our genetic material. All the DNA in a cell constitutes the cell's genome. So this means that inside of the nucleus, I'm going to use eukaryotic cells because that's what we're mostly talking about right now.
In a eukaryotic cell, you have a nucleus. And inside of that nucleus, you have DNA. And all of the DNA that's in there represents an organism's genome. So genome is all of the DNA that makes up that particular organism. Now for humans, our genome consists of 46 chromosomes.
Okay, that's our magic number for humans. It's different for every organism. All right, this means that you got 23 from your mom and 23 from your dad, and you're kind of a mixture of the two of them, but you have 46 chromosomes in all of your cells.
Okay, the genome... I just want to point out is every single one of these chromosomes and it's present in all of your body cells. Okay, so a genome can consist of a single DNA molecule in a prokaryotic cell or a bunch of DNA molecules in a eukaryotic cell. Okay, and DNA molecules are packaged into chromosomes.
So chromosomes are just packaged DNA. So chromosomes, we're going to talk about this in a little bit, but chromosomes are actually made of chromatin, but it's just highly organized DNA. So we use those two words like synonymously in this whole thing.
This is kind of like a creepy looking eyeball, but what it is, is it's a cell. And this part is representing the nucleus for you. And then all of these little purple squiggles and things in here are representing all of the compact.
chromosomes. So that's the whole genome is present inside of this little nucleus here. So that is all the directions that it takes to make whatever organism the cell is from.
So our eukaryotic chromosomes consist of something called chromatin. Okay and it is just simply DNA and protein. That's it.
So chromatin, what is it? It's DNA and it's protein and that's what makes up a chromosome. Okay so chromosome is made of chromatin.
Chromatin is DNA and a protein and a couple proteins. Okay, so every single eukaryotic species has a characteristic number of chromosomes inside of each cellular nucleus. So for us, that's 46. Again, that's our magic number. Okay, and our somatic cells, which are also body cells, we have, this is our diploid number. Diploid, which means two sets.
These are our non-reproductive cells, so they make up your body, and you have two sets of chromosomes. Again, that's called diploid. Di means two, so you have two sets of chromosomes.
You got one from mom and one from dad that makes up your two sets. Okay, this means that we have 46 chromosomes in our body cells or our somatic cells. All these words mean the same thing.
Okay, and our gametes, which are going to be our sex cells, we only have half that number. These are the reproductive cells. You know that sperm cell plus an egg cell, going to equal baby. Alright, so this means that we have 23 chromosomes plus 23 chromosomes is going to equal a baby, which is 46, because that's how many chromosomes are in our human cells.
Okay, so this is only one set of chromosomes, which is why you get one set from dad, one set from mom, and then you have two sets. So that's how all of that works. All right, let's talk about the distribution of the chromosomes during all of this eukaryotic cellular division that's going on.
So in preparation for cell division, the DNA has to be replicated. Remember that replicated means to make a copy of. We're going to make a copy of it.
Okay. And we're also going to condense it or pack it tightly together. Okay. Each of these duplicated chromosomes has two sister chromatids. This is going to get a little bit wordy, but I promise the pictures will make sense.
Okay. And these are joined identical copies of the same original chromosome. So we're going to look at a picture in just a second.
It's going to make more sense. Now, these two sister chromatids are held together by a centromere. And that's where the two chromatids are actually attached to each other.
So let's just look at a picture because this is a lot of words. Okay, this whole thing here is typically called a chromosome. And it's composed of two sister chromatids. So you have a chromatid here.
And you have a chromatid here, okay? They're sister chromatids because they contain the same information, okay? So on either part here, it's showing you up and down.
It's the same information. It's a copy, okay? And then the centromere is what binds them together. It's what's holding them together to make this little X-shaped unit, right?
That's called a chromosome. All right. So during cellular division, these two sister chromatids, which we just looked at, looks like this. The two sister chromatids of each duplicated chromosome separate and move into two nuclei.
So these are going to come apart, they're going to separate, and then they're going to move away from each other into two separate nuclei. Once they're separate, they're also called chromosomes. So this gets a little bit confusing, but don't worry, there's pictures. So this little guy up here, this little purple one, he's called a chromosome. When we duplicate during the S phase, which we'll talk about in a little bit, you have the chromosome duplication, which means that you make a copy, right?
So you have the original and you have a copy. Okay, these are your sister chromatids. And remember that they're held together by the centromere.
Okay, and then they are separated into two different nuclei and these again are called chromosomes. So it's a chromosome up here and these are chromosomes and these are sister chromatids in the middle. Alright, so eukaryotic cell division consists of two main parts. The division, right, cellular division is mitosis, that's part one, and then cytokinesis.
So mitosis is the actual division of the nucleus essentially. So we're dealing with genetic materials or DNA. So this is the division of the DNA in the nucleus.
Cytokinesis is division of the cytoplasm. So this happens later in the process. Okay. So you have to first divide the nucleus and then you can divide the cytoplasm. Our gametes are produced kind of in a similar way.
It's a type of cellular division and it's called meiosis, which is basically mitosis, but it happens two times and we'll talk about that later. Okay, so meiosis is going to make non-identical daughter cells and remember that mitosis is going to make identical daughter cells. I like to say identically because I keep forgetting that it's genetically identical.
All right, so the mitotic phase alternates with the interphase of a cell cycle. So let's talk about that. So the overall cell cycle, it's a cycle, so it's a circle, all right? You have just a very small portion of that that's actually going to be mitosis, okay?
This whole part here... called interphase and that is about 90% of this well about 90% of the cells life which means that mitosis is only about 10% okay so in order to find out where is the cell in this whole cycle Walter Fleming developed a dye that lets you look at the chromosomes and that tells you where you are. Are you in mitosis?
Are you in cytokinesis? Or are you in this other whole thing that's called interphase? Okay, so this dye allows you to actually look at the chromosomes and determine by their shape and where they're located in the cell, where the cell is in the cell cycle, which is actually pretty neat.
We still use that today. All right. So the phases of a cell cycle, there's two words there, two phases.
All right, you have interphase, which comes first and mitosis, which comes second. So interphase is where the cell is going to grow, it's going to copy chromosomes and prepare to divide. And then during the M phase, the mitotic phase, the process of mitosis, you have mitosis and cytokinesis, which is the actual cellular division part. So interphase is the longest part of the cell cycle.
So it's going to make up about 90% of the cell's life and it's actually divided into three different parts. So it's the G1 phase, the S phase, and the G2 phase. And the key player here is going to be synthesis, which means to make. And we're going to talk about that in just a second. Okay.
So basically the cell's growing through this whole process. Okay. All of interface, the cell's growing, the cell's doing its daily function. If it's a little red blood cell, it's carrying around oxygen, it's exchanging for carbon dioxide.
It's bringing it. facts, your lungs, right? It's doing its little cellular job. That's what it's supposed to be doing. And this is when it does it.
It's also growing and also preparing to divide. And during the S phase, it's going to be duplicating the DNA. Okay.
So let's talk about this. You have one cell and you're trying to take that one cell and you're trying to turn it into two cells because that's the point of mitosis. Okay.
That one cell contains 46 chromosomes. Okay. Now for those of you that see where this is going, if you don't ever duplicate that DNA and you just take 46 and you divide it into 23 and 23, you do not have a genetically identical daughter cells to the initial, right? So during the S phase synthesis, you're going to double the DNA to make 92 chromosomes in that one cell in interphase once you hit the S phase.
Okay, because then later in mitosis, when you actually go through cellular division, you'll end up with 46 and 46. That's a human, human, and human cell, right? That's correct. That's what you want. Now, let's just say if you took that 46 and you just split it into 23 and 23, well, these are not genetically identical. And this is a haploid cell, which is a sex cell.
And that's not what we're trying to make here. We're trying to make more somatic cells or our body cells, right? So the whole point of the S phase is to double that DNA. And that's so you get the correct outcome at the end with our 46 and 46. So interphase is 90% of the cell's life cycle.
It has three different parts, G1, S, and G2. And the S phase is very important because that's where we're doubling the DNA. So as I said, interphase is this huge part.
This is about 90% of the cell's life. You have G1, which is growth. You have the DNA synthesis happening in S phase.
Again, that's where we have 46. And we turn that into 92 chromosomes. And then you go through G2, which is really like a preparation step because you're about to divide. So if you see G2.
goes immediately into mitosis. It just goes immediately into there. So this is a preparation step to get to mitosis. Of course mitosis is only about 10% of the cell's life and if you remember up here we created the 92 chromosomes.
When you come back around and you create those two cells at the end each of these is going to have 46 chromosomes and that's exactly what we want. So let's talk about the actual steps of mitosis. So mitosis...
actually cellular division, right? That's where we're actually going to see the division occur. So it's usually four phases.
This textbook uses five phases, which is fine. Usually it's PMAT, prophase, metaphase, anaphase, and telophase. Okay, prometaphase is just like in between the prophase and metaphase. It's kind of like an in-between step, okay?
I'm just going to teach you I teach this as PMAT. PMAT. So mitosis the order is PMAT.
So I like to teach prophase packed, metaphase middle, if I can write an M that would be great, anaphase apart, and telophase two nuclei in the same cell. Okay, this will make sense when we look at the pictures. But you see the alliteration, prophase, pact, metaphase, middle, anaphase, apart, telophase, two, like T-W-O-T for two.
Oh my God, look at that. All right, that's how I like to teach this because I think it helps you remember things the best. And then of course, cytokinesis is going to happen later in mitosis. I teach that it happens during telophase.
They happen simultaneously. Some textbooks will also say it happens in anaphase. For the intents and purposes of what I teach, I teach telophase.
All right, so let's look at this. So G2, remember we said that this is a preparation step, okay? Because that's right before we go into mitosis, which we have the first step is prophase. Okay, so G2 is just preparation. We make sure that we have our centrosomes.
These little guys are called asters, like this whole little, this is called an aster. Okay, these little guys in the middle are your little centrioles. Okay, that's where the microtubules are going to grow out of. You can see them right here.
Okay, that's where the microtubules are going to grow out to attach to our chromosomes to pull them around the cell. Okay, but basically, you have prophase first in mitosis. Prophase is packed. Okay, what's packed?
Your DNA. Look at it here. It's like loosey-goosey spaghetti. And over here, you can see that you have your little duplicated... Sister chromatids being very organized.
Okay, it's organized You have packed DNA. So I like to teach prophase is packed. Does other stuff happen here?
Yes, of course Okay, you start to have the Dissolution of the nuclear membrane and other things like that But I like to teach prophase packed because it's always going to ask you to identify it in an onion root tip cell And it's always when we have very tightly packed chromosomes The next one is the in-between step pro-metaphase. I'm going to skip it for just a second and go to metaphase. So remember that metaphase, our word was middle. Do you see why it was middle?
Because they're in the middle again. Okay, so the chromosomes are now lined up in the middle, and you can see that these little guys, the microtubules, microtubules, pushed and pulled them into place. So they attached to them, and then they pushed and pulled them into place.
Okay, so basically between prophase and metaphase comes prometaphase, which is just an intermediate step. And you can see that you have the connections being made. You have the microtubules starting to push and pull these chromosomes into place.
You can see a little bit of our nucleus still remaining in the background as it's starting to dissolve and go away. It's just between these two stages. So I just like to teach prophase is packed, then you have this random intermediate step, metaphase in the middle.
In anaphase, our chromosomes are being pulled apart. again, apart by our microtubules, okay? The little yellow guys, microtubules.
So you can see that you have your sister chromatids that are now separated, right? They're no longer together. So now these are called chromosomes again. So your sister chromatids separated and now are chromosomes again, okay?
So our last step here is going to be telophase. And remember that telophase is two nuclei. the same cell. So you can see that here it's kind of like this lumpy figure 8. It's all one cell and you have two nuclei that are forming here and here.
Okay two nuclei in the same cell. Alright there's a little hand model that I'll do another video on and show you how that works but you have two nuclei you actually hold up little binoculars to your eyes. Okay So you start to see something called the cleavage furrow forming, and that's this little constriction ring that's going to help to pinch off the cytoplasm for cytokinesis.
Okay, so the cleavage furrow is actually a part of cytokinesis that helps to pinch off the cytoplasm. All right, so we're going to take a little bit of a closer look at all of this. So the mitotic spindle is a structure that's made of these microtubules, the little yellow guys that we've been talking about.
Okay. And it helps to move the chromosomes during mitosis. And I've been saying that this whole time.
Okay. So in animal cells, the assembly of our spindle microtubules start off in the centrosome, which is the microtubule organizing center. So basically back up here, this is when we started talking about the centrosome. Okay. The centrioles are those little like cylinders that are inside.
The whole thing is also referred to as an aster. And then our early mitotic spindles, again, these are our microtubules. Okay, so that's what we're referring to there. Okay, so it controls the movement of the chromosomes during mitosis.
And the whole thing starts off from the centrosome. So the centrosome replicates during interphase, okay? forming two different centrosomes that migrate to the opposite ends of the cell during prophase and prometaphase, prophase and prometaphase.
So let's go back and look at those. Okay, so during prophase and prometaphase, you can see that you have two centrosomes that are starting to separate. And now they're on opposite ends of the cell. Why is that important? Because as the cell grows and elongates, now you'll have one in each cell when they split, which is what you want, because you replicated them during interphase.
Alright, so we talked about the aster already and the spindle is going to include the centrosome, the spindle microtubules, and the asters. Alright, so during chromatophase, that's our in-between step, some of the spindle microtubules are going to attach to kinetochores of the chromosomes. Okay, and they're going to start to move the chromosomes around. So kinetochores are just these proteins that exist on the DNA at the centromeres.
So if you remember that you have sister chromatids that are joined together by centromeres, okay, there's also like little accompanying little guys on the outside and those are your kinetochores. So if you go back here and you can see they're little dots and I kind of drew over them, okay, but here you can see that you have this little dot here, you have this little dot here, right? Those are our kinetochores that the spindle is actually attaching to in order to help separate the chromosomes and that's really important. because if they're attaching in the correct spots, then you know that when you separate, you're separating the chromosome, the whole thing, the sister chromatids, you're separating them equally.
So you don't have like, you know, your little sister chromatids and you have one spindle attached here and one attached here. It's not going to pull it apart evenly. So you're not going to have genetically identical daughter cells here. So it's really important that they attach to those kinetic cores and split them evenly.
At metaphase, the centromeres, of all the different chromosomes are at the metaphase plate because remember that they're all like lined up along the center of the cell and That's like some imaginary structure that's between the two poles before they actually get split and pulled apart Okay, so this is kind of what we've been talking about here You have your little kinetochores, which is where you can see all of your spindles attaching and then again It's important that they attach there so they split everything evenly Next in anaphase, remember that anaphase is apart. What are we pulling apart? The sister chromatids. They're going to separate and move along the kinetochore microtubules, so those are the ones that are attached to the kinetochore, makes sense, towards the opposite ends of the cell, right?
Because you're going to start to form your two new nuclei. So you're going to be separating the sister chromatids into singular chromosomes that will then recondense in the nucleus that's going to be formed. Okay, so in order to pull the chromosomes apart, the microtubules actually have to shorten. So depolymerization or depolymerizing, remember that a polymer is a large molecule.
D means like undoing it, okay, or like against. So depolymerizing, depolymerization is just going to be basically you're taking away little segments of the microtubules as you go throughout this process. So essentially the chromosomes are being like reeled in by these things called motor proteins that are at the poles of either cell as these microtubules are starting to kind of be deconstructed. So this is what we're talking about here. Okay so in this first picture you have this is an experiment that was done at some university in like Wisconsin.
They wanted to know whether the kinetochore microtubules actually depolymerize at the kinetochore end or the pole end. So they weren't sure if they were like getting smaller on this side or on this side. So they did this experiment and they put like a mark and then they were able to tell.
Here you can see the mark that during anaphase. So this is all showing you anaphase because you're pulling the chromosomes apart, the sister chromatids apart. the chromosomes are moving correlated with the kinetochore microtubules.
So as they're shortening their kinetochore at their kinetochore ends, not their spindle pole ends. So actually where they're attached here, right, is actually where they're shortening, not at the other end. OK, they're actually releasing these little subunits of tubulin, which is what a microtubule is made out of. And that's how they're able to shorten.
So our non-kinetic or microtubules from the opposite sides of the elongated cell are actually helping to elongate the cell. OK, and then at the end of anaphase, so after we've split our sister chromatids apart, duplicate groups of our chromosomes have a ride of the opposite ends of the elongated cell, which means that now, like, you know, as we're moving into telophase, we're going to start to develop those two nuclei that we were talking about within the same cell. Okay, so then the spindle fibers and all of the apparatuses there start to kind of go away. They're disassembling as we have the restructuring of these nuclei during telophase because they're not needed anymore. So cytokinesis, remember that that's the division of the cytoplasm.
Okay, and this is going to occur by a process known as cleavage. and it forms a cleavage furrow. So it's kind of like that little like figure eight. There's this little ring here that's like this contractile ring. It's called the cleavage furrow.
When you actually look at a picture of it, it kind of looks like a butt. Okay. And that actually pinches in to pinch off the cytoplasm.
So then you can form your two genetically identical daughter cells. Whereas in plants, because remember that plants have a cell wall. So if you just kind of try to pinch on the cell wall, it's not going to work.
correctly. So essentially you have to rebuild a cell wall in the middle of this really elongated cell and it's called a cell plate. So we're going to look at those.
See, I told you it looks like a butt, right? The cleavage furrow, which is right here, it's pointing to it for you, right? Kind of looks like a butt.
It's a contractile ring made of microfilaments that just starts to form and then pinch. And as it pinches off, you have your two genetically identical balls. daughter cells.
Whereas in a cell plate is utilized in our plant cells. These are in our plant cells. Because our plant cells have this cell wall. So you have to start to form the new cell wall to actually split the cells. And so you have these little vesicles that form the cell plate.
And then once they are fully formed, then you have your new cells. So this we've kind of been talking about this in animal cells, but this is what it actually looks like in our plant cells. And this is typically what you're going to be asked to like identify when you're dealing with like test questions of actual pictures here. So in prophase, you can see that you have very packed. chromosomes.
In prometaphase, remember that it is just like an in-between step between prophase and metaphase. It kind of looks like a mix between the two of them. Metaphase, remember that your word is middle, that you can see that you have your chromosomes lined up along the middle of the cell. And then in anaphase, your word is apart. So you have the chromosomes starting to separate apart.
And then in telophase, you have two nuclei in the same cell. Right. So here's one here. Here's one here. And then here you can start to see all those little vesicles that are forming your cell plate, because then once that actually solidifies is when you have the complete division of that cell.
My dog is chewing on a ball underneath me. I'm sorry for the squeaking. So, like I said, binary fission. I think I mentioned it earlier. If not, this was that asexual reproduction I was talking about.
Binary fission is what happens in bacterial cells. So bacterial cells are unicellular. They're also kind of weird so I'm sure that there's like one or two that are an exception to the rule but typically they're unicellular.
So binary fission is how they reproduce. So prokaryotes, bacteria or archaea, just like eubacteria from the kingdom, eubacteria or archaea like older ancient bacteria reproduced by a type of cell division, it's called binary fission. Okay, so this is actually how they're creating more of their own selves essentially.
They're copying themselves. So in E. coli, which is a really common bacteria, the single chromosome that they have, remember, it's a single chromosome because they're bacteria, they're prokaryotes, it's really common, is going to replicate beginning at the origin of replication, which makes sense. And it kind of goes around in a circle. Okay.
The two daughter chromosomes actively move apart while the cell elongates. So the cell is going to elongate and you'll have like two copies split there. And then the plasma membrane is going to pinch inward, dividing the cell into two different parts.
So here's essentially what's happening there. So you have your chromosome in the middle. You have your two copies because you're going to replicate it at the origin of replication. Here you have one copy of DNA, one copy of DNA. And then the cell starts to pinch off here to create two new cells.
asexual reproduction, right? That's how it happens. And again, this process is called binary fission. Bi means two and it makes two cells.
So there you go. Okay. The evolution of mitosis is actually really interesting.
So you know that prokaryotes came first because pro means before nucleus. They came first. They were the first cells.
Evolved before eukaryotic cells. So mitosis actually came from binary fission because this occurred first. If our prokaryotes came first, binary fission is actually an older process, a more conserved process.
So mitosis evolved from binary fission, which they happen very similarly. So it's really interesting actually. And we have certain things, protists, protists are kind of like the gray area of biology that I hate.
They break all the rules, but whatever. like dinoflagellates, diatoms, and some of our yeast cells even that are going to exhibit different types of cellular division that seem to be some sort of in-between or intermediary step between binary fission and mitosis because remember that this came first whereas mitosis evolved later at some point. So it's kind of believed that these mechanisms are kind of like the in-between like to show that evolution has occurred here that dinoflagellates and diatoms have these different mechanisms of replication.
So in dinoflagellate, they're unicellular eukaryotes. The chromosome is actually attached to the nuclear envelope. So that's like around the nucleus, right? Which remains intact the whole time during cellular division.
And our microtubules are going to pass through the nucleus inside of these little like cytoplasmic little tunnels that are going to help to reinforce the spatial orientation of the nucleus to keep its shape and everything. which then divides in a process that kind of resembles binary fission, right? So this is sort of like a derivative here that we just that we see in dinoflagellates. Then with like diatoms and some of our yeast cells, it's a little different.
These are also unicellular eukaryotes and the nuclear envelope also stays intact the whole time. And in these organisms, actually, the microtubules form a spindle like apparatus inside of the nucleus. And then these microtubules separate the chromosomes and then the nucleus splits into two different daughter nuclei, which again is really similar to the processes that we know today to be occurring in our cells. Okay, so how does all of this happen?
How does your cell know that it's time to divide and how does it know to go from one stage to the next stage? Okay, so the frequency of our cell division is going to vary with cell types, right? Each cell has a different lifespan and obviously some are going to be shorter than others which means that they're going to be going through cellular division more often than other types of cells. I think your red blood cells have a pretty short lifespan overall, right? And so these differences are going to result in regulation of on the molecular level.
So like within the cell. So cancer cells are the exception to this. And we're going to talk about cancer at the end of all of this, because it's the exception to the rules that we're talking about here. So they managed to like escape or kind of like disregard all of these controls that we have in place in order to help us maintain the fluid, you know, motion of our cell cycle.
Okay, so essentially on the molecular level, scientists believe that we have cytoplasmic signals that actually control when you go from one stage to the next stage and so on. So the cell cycle is driven by specific signaling molecules that are present in the cytoplasm. That's where those cytoplasmic signals come from, okay? They're these little molecules that are in the cytoplasm that kind of like, hey, you need to do this now, right? So some evidence for this.
hypothesis came from an experiment with these mammalian cells where they cultured some connective tissue, which we'll talk about in just a second. There's a picture of it coming up. So cells at different phases of the cell cycle were fused to form a single cell that has two nuclei at different stages. So they have one big cell and they took, you know, it had a nucleus in it.
They took another nucleus and put it in there and maybe... this one thought that it was in the S phase, whereas this nucleus was currently like in the G2 phase or something. And then they kind of wanted to see like what happens. Because if this is the nucleus that belonged to this cell, then in the cytoplasm, there should be all these little signals that tell it like you should be in G2, bro.
Right? So we're going to look at all of that. So these cytoplasmic signals from one cell could potentially cause the nucleus from a second cell to go into the wrong stage of the cell cycle. So this is an experiment that was done that we'll talk about right now. So experiment one versus experiment two.
Basically what's happening here is that these researchers in Colorado were wondering whether the cell's progression in the cell cycle is controlled by these little cytoplasmic molecules or not. So in order to research this, they selected cultured mammalian cells. that were in different phases of the cell cycle and then like forced them to fuse with each other and the two experiments were shown are shown in this picture here right so you can see that this is what happened here and this is what happened here so when you fuse an s s phase nucleus with a g1 phase nucleus you get all s phase nucleus or nuclei right in experiment two you can see that you have an m phase so mitosis, and G1, which is way at the beginning of interphase, right?
And then it forces them both to go into mitosis. So here, the G1 nucleus on this side, experiment one, the G1 nucleus immediately entered the S phase, and DNA was synthesized. And then in the experiment two, our G1 nucleus again, the nucleus began mitosis without chromosome duplication, okay?
So these little cytoplasmic molecules. do control that, right? So molecules that are present in the cytoplasm control the progression to the S phase and to the M phase, right? The S being synthesis, right?
So there's at least something going on that's pushing you towards synthesis and towards mitosis. So we also have these little things called checkpoints, okay? checkpoints of the cell cycle control the whole process or the whole system.
So we have a series of events of the cell cycle that are directed by these discrete and distinct cell cycle control systems, which is similar to sort of like it compares it to the timing of like a washing machine that your washing machine has like, you know, it has like the rinse cycle and all of that there's all these different stages. And it just keeps repeating when you do a new load of laundry, right? So the cell cycle control system is regulated by both internal and external controls or forces. So we have specific checkpoints where the cell cycle stops until a go-ahead signal is received.
And that's the G1 checkpoint, which we'll talk about in just a second. Right. So we have these both internal and external controls. The internal control that we just talked about, the cytoplasmic, cyto.
plasmic signals. We just talked about those and we're also going to talk about some external ones here in a little bit. Okay, but there's three main checkpoints. So the G1 checkpoint, you have the G2 checkpoint and the M checkpoint for some reason, I can't draw down here, but that's fine. Okay, so there's those three checkpoints.
The G1 is known as like the go ahead checkpoint. Like if it goes here, it's typically going to continue all the way through the cell cycle. Okay, so for many cells, the G1 checkpoint seems to be the most important. Like I said, if a cell receives a go-ahead signal, so that's the G1 checkpoint, if it gets to there and it's like, yep, go ahead, you can move on through, it'll usually complete the entire cell cycle and actually go on to division.
Okay, so if the cell does not receive a go-ahead signal, it goes into something called the G naught phase. So essentially here, if you are stopped, then you... leave and you go to a cycle of g-naught and we'll talk about that in a minute.
That's a non-dividing phase. Okay so g-naught phase is non-dividing and actually a lot of our cells go there. Most of them can be pulled back but like as you get older it kind of sucks that you can't pull back like your mature nerve cells or mature muscle cells because they stop dividing.
So actually most of the human body cells are in the G-naught phase, but they can just be pulled back, especially if there's some sort of like growth factor that's released during some sort of injury or something, then it pulls them back very quickly to make sure that you repair those tissues. So here's a little bit about those checkpoints. So like I said, like a red light or green light sort of thing. If you get a red light up here, you're going into G-naught, which is a non-dividing stage.
Okay, so in the absence of the go-ahead signal, if you get that red light that says, no, not going through here, the cell is going to exit the cell cycle and it enters something called the G-naught stage, which is a non-dividing state. Like I said, it can be pulled back in some cases. Okay, and then over here, you get the green light. The cell receives the green light, go ahead.
It's going to go on. It's going to continue the cell cycle, right? And then down here at the bottom, we've got the M checkpoint.
This means that you've already gone through the G2 checkpoint. Like you're already, you already drove past that. You're in the clear, right? So a cell in mitosis receives a stop signal when any of the chromosomes are not attached to spindle fibers, which is important because you want to make sure that you have your chromosomes splitting equally, right? And then over here, if you get the green light, when all the chromosomes are attached correctly to the spindle fibers.
from opposite poles of the cell, the go-ahead signal is going to allow that cell to go ahead and proceed into anaphase because that's where the chromosomes are split. Right? So you need to make sure that everything is lined up correctly, that all the spindles are attached correctly, and then you can go ahead and split in anaphase. So that's what's happening with all the checkpoints.
The cell cycle is also regulated by a set of regulatory proteins that are called kinases. So you know that kinases function with phosphorylation. That's correct. So they work on these proteins called cyclins.
And you have CDKs, C-D-Ks, cyclin-dependent kinases. Okay, so basically you get different fluctuations. We're not going to go too much into it. But you have different fluctuations of like you have a lot of a particular kinase as you go.
towards the next stage of the cell cycle. Basically, they like go up and down as you're moving towards the end of mitosis, right? So they're pushing you through. That's about all that you need to know about those. We're not going to focus on that a whole lot, right?
But you have these things called CBKs. They're kinases. They're cycle-independent kinases that are going to help push the cell. It's another internal mechanism that's going to push the cell to the next stage. Okay, so an example of another internal signal that occurs during the M phase checkpoint.
So in this case, the anaphase does not begin. If our kinetochores aren't attached, we just kind of talked about that with the M phase. Remember that the kinetochores are on the outside of our little centromeres. If you don't have a spindle fiber, like a kinetochore microtubule that's attached to that correctly, then you're not going to go through, right? Attachment of all of the kinetochores acts.
activates the regulatory complex, which then activates the enzyme separese. And separese allows these sister chromatids to actually separate. Makes sense.
And you know that it's an enzyme because it ends in A-S-E and it's allowing you to separate, which is helpful, which is going to trigger anaphase. Because then remember, we're going to take these and we're going to split them apart as we pull them to opposite ends of our cell. We have external signals as well that are helping to control the cell cycle like growth factors Which are proteins that are released by certain cells that stimulate other cells to divide Essentially it works like this if I am a cell and it is my turn to divide I'm going to release Signals that tell the cells around me. Hey, yo, don't divide it's my turn right now, right? And then when I'm done, I'm going to release growth factors that tell the other cells to divide because like hey man, I'm done it's your turn now.
Okay, and we do this because remember that the cell cycle, only 10% of it is mitosis. And if I am here, and every other one of the cells around me that's doing the same job as me, we're all here at the same time. Well, then no one's doing this.
And remember that during interphase is where the cells actually doing its job. I mean, yes, it's growing. But this is where it's doing its job. If its job is to help supply oxygen to the body and all of us decide to divide at the same time, the person's going to die. And that's really bad.
So this is why cell communication is important. We have this particular example that we're going to talk about. Platelet-driven growth factors, PDGF, is going to help to stimulate the division of human fibroblast cells in culture.
So we're actually going to look at a picture of what this looks like here. right so essentially we have these things called PDGFs okay and they um this experiment is going to demonstrate that these PDGFs are required for cellular division of fibroblasts and fibroblasts are these little um cells that make up our connective tissue okay so these fibroblasts have PDGF receptors in their plasma membranes right so around the outside so when these little PDGF molecules bind to the plasma membrane, these little receptors, it's going to signal like this little pathway that allows the cell to pass the G1 checkpoint and then go through division. Because remember that G1 is like the go ahead. And if it goes through that, then it's going to divide, right? So PDGF stimulates the fibroblast division, not only in artificial conditions, but also in the actual animal body.
So this happens in our bodies. And then when some sort of like injury occurs. the platelets are going to release PDGFs in the vicinity, which are going to be like, hey, you need to start making more cells to help heal this wound. And that's basically what's happening here. So you can see that you have a sample of human connective tissue that's cut into small pieces.
The enzymes are going to be used to digest the extracellular matrix, which just leaves these free floating cells, the fibroblasts. And then the cells are transferred to different culture vessels. So you have one without PDGF, which tells it divide and then the other one with PDGF which you can see you start to replicate these cells or starting to you know repair that tissue so that's how that works. Another example of these external signals is density dependent inhibition in which crowded cells stop dividing.
So if you have I mean, it's density dependent. So density, like how many of them are in this given area. So if you have a whole lot of cells in the given area, it's basically going to create like some sort of like pressure that makes the cells stop dividing, right?
Because when you have uncontrolled cell growth, uncontrolled cell growth, what's that called? It's called cancer. All right.
Whether you have just like a tumor that's created or like actual cancer, right? When you have uncontrolled cell growth, that's what that leads to. So this density dependent inhibition is like, hey man, there's a whole lot of cells in this little area. We don't need any more of you right now. Why don't you go ahead and stop making more cells?
And that's what happens. And we also in mammals, well, all animals, but I'm going to use mammals because we're mammals. In all animals, these cells also go through.
anchorage dependence. So anchorage, think about an anchor, okay, being like bound to something, okay, have to be attached to something. It says substratum, just something. It needs to be attached to something in order to divide, okay? Where do you think this comes from?
If a cell needs to be attached to something in order to divide, why is that important? Okay, think about a fetus. Think about a fertilized egg.
that is one cell, right? And you had your little sperm cell fertilize this egg. This is going to float around until it ends up inside the uterus, which is kind of like an upside down pear. Okay.
And when it hits that nutrient rich lining of the uterus, it's going to attach and then it's going to start dividing. So anchorage dependence is actually incredibly important because if our cells did not have this requirement, then it would be very difficult to have tiny humans running around. Okay, so this is actually really cool.
So anchorage dependence means that you need to be attached to something in order to divide. So you can grow cells like in a laboratory by attaching them to a surface. your cells grow in your body by attaching to a surface or to each other right and this like I said it stems from a fertilized egg knowing to start growing when it attaches to the uterine lining because in all of this blood is a whole lot of nutrients that the growing fetus can can rely on right and so the important thing that we're going to talk about here is these cancer cells these bad guys exhibit neither neither density dependent inhibition nor Anchorage dependence.
So they don't stop dividing when there's a whole lot of cells and they don't need to be bound to something to keep dividing. So this is where we get that uncontrolled cellular growth called cancer. Okay.
So here's an example. Hello. Hello. Okay. Here's an example of the same tissue happening with our cancer cells.
So normal mammalian cells. We just kind of looked at the same sort of like experiment like here when you have like the signal to like go ahead and do this. Great. OK, so down here, our anchorage dependent cells require a surface for division. Great.
You put the cells on the plate. They divide. Perfect. That's correct. OK, you take a couple of them away and they should fill in the gap and then stop.
OK, so they fill in the gap. Rude. And then they stop. And cancer cells, they don't stop. They just keep going.
This is uncontrolled, right? This is uncontrolled cell cycle happening all over the place. Screw the checkpoints.
We're dividing no matter what. That's exactly what's happening here. Uncontrolled cell growth. And it leads to the formation of a tumor, which is a mass of cells.
Okay. So the loss of cell cycle controls and cancer cells. So cancer cells do not respond to any signals that normally regulate our cell cycle. They don't.
respond to any of those little molecules that are in the cytoplasm that are telling you what to do. They don't respond to cyclin-dependent kinases. They don't respond to checkpoints and things like that.
Cancer cells may not need growth factors to grow and divide. They're just like, nope, screw it. We're growing and dividing.
Thanks for your opinion, but I don't care. Right? So they make their own growth factors that are like, ah, I'm going to keep dividing.
And I'm going to tell all the other cancer cells around me, they need to keep dividing too. That's why it's just kind of gets out of control really, really quickly. They may convey a growth factor signal without the presence of a growth factor.
So they may be able to activate these receptors in their membranes that tell them to divide. And it's like, yep, okay, even though there's no growth factor there. And they may also have an abnormal cell cycle control system. Rude. There are so many types of cancer.
We don't know all of the different nuances of what's going on with all of them because there's so many different types and it's so unique to each individual person. But there's something abnormal going on with how they're controlling their cycle versus a normal cell going through the checkpoints and the cyclin dependent kinases that are helping to push the cell into different stages and things like that. A normal cell is converted to a cancerous cell by the process of transformation. So the cancer cells... That are not eliminated by the immune system form tumors which are masses of cells These are abnormal cells that don't follow the normal rules of a of a cell cycle Okay, so if abnormal cells remain at the original site and they just have like one lump.
They're called benign It's spelled weird benign tumors. Okay, so this is not that bad Okay, this is not that bad Malignant tumors are the bad ones. They invade surrounding tissues and can metastasize. Metastasize is a bad thing.
Metastatic cancer is a bad thing. This means that the cells are able to go to other parts of the body where they can form additional tumors. These are the ones that you need to look out for.
The malignant and metastatic tumors. Those are the bad ones. Benign ones just means that you had some cells that kind of a little haywire, but it's not dangerous.
the malignant ones are the ones that start to invade other tissues. They're growing at such a rate that they're starting to encroach on other territory and affect your tissues that they're not necessarily present in. Then they can break off from those tumors and cause tumors in other areas of your body, which makes it very difficult to find all of them and get them before something, you know, before they just kind of like take over, right? So here's kind of an example of all of this.
So we have the growth and metastasis of a malignant breast tumor. So the cells of a malignant cancerous tumor grow in an uncontrolled way and then they can spread to these neighboring tissues in the lymph and blood vessels and other parts of the body once they metastasize. So you can see that a tumor is going to grow from a single cancer cell. So a tumor is a massive...
cells that have uncontrolled cell division. And then you see in number two the cancer cells invade neighboring tissues. So it's not just this one area that's being affected now.
It's multiple areas that are being affected. And then the cancer cells are going to spread through the lymph and blood vessels to other parts of the body. So if one little tiny cell, one of these cells breaks off and ends up in the bloodstream.
then it's going to go plant itself somewhere else and start to grow more tumors there because that one cell is going to become two cells and those cells are going to become four cells and so on and so on and so on because that's how mitosis works. It's making these copies exponentially over time, right? And then that's when you have this metastatic tumor because the small percentage of the cancer cells metastasize, right? They moved to another part of the body and started to form a new tumor, which is really dangerous.
Okay, recent advances in understanding the cell cycle and cell cycle signaling have led to advances in cancer treatment, which is a great thing. But like I said, cancer is so hard to treat because it's so unique. Because it's typically something in your DNA that's gone wrong that made your cells escape the control mechanisms of the cell cycle. So every single person's DNA is different. So how do you come up with a treatment for like almost 8 billion people?
No one thing is going to work for everyone. And there's a whole bunch of different types of cancers, which creates another problem. problem, right? So we're discovering new things all the time, but the key is going to be all these different ways that they're escaping the cell cycle and maybe some way to turn those regulations back on to prevent the spread of cancer.
Medical treatments for cancer are becoming more personalized to an individual patient's tumor. That's like what I was saying. One of the big lessons in cancer research is how complex cancer is. Like I said, it's based on your DNA a lot of the times.
It's a genetic mutation or some sort of acquired mutation. that you've gotten in your life that's caused your DNA to be damaged. And then that's your DNA. It's not the same as anyone else's.
It's very difficult to come up with these personalized treatments. But there's a lot of progress being made in that every day. If you want some sort of really awesome molecular biology job when you get older, definitely go into cancer research because it is very interesting.
It is very sad. But when you can find something to help someone, that is so, so, so rewarding. So that's going to do it for our sales cycle.
I hope that that answers some of y'all's questions about it. Thanks for sticking with me. I'll see you in the next one.