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PAGE 1 OF 13 Chapter 5 The Cellular World | A Manifestation of the Macromolecular World Module 1 | Transitioning to the Cellular World Lesson 1 | The Cellular World | Where it All Comes Together As we've seen so far, with each level of scale comes a new level of complexity: from subatomic particles to atoms, from atoms to molecules, and from molecules to macromolecules. Naturally, adding another level of scale on top of this as we zoom out and look at cellular structures increases the level of complexity again. The cellular world may look very different from what we've seen so far because as we zoom out, objects become smaller and biological processes therefore look to be more fluid. However remember that the cellular world is built from nothing more than the macromolecules that we have learned about: proteins, polysaccharides, nucleic acids, and lipids, all working together in a very mechanical way. In other words, when we look at cellular function we're really looking at the manifestation of the collection of macromolecules working together in the macromolecular world. In fact, we've already had glimpses of the cellular world when we learned about some of the mega-complexes like NPCs, focal adhesions, the flagellum, and the lamellipodium. The cellular world is fascinating because it allows us to have a clear view of both the macromolecular level below upon which the cell is built and also to see how different cellular structures and compartments work together for the overall function of the cell. One important point to keep in mind throughout this chapter is that although we will usually show cellular structures and macromolecules without the surrounding solution, remember that everything we see, both intracellular and extracellular,

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Page 1: Chapter 5 The Cellular World | A Manifestation of the

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Chapter 5

The Cellular World | A Manifestation of the Macromolecular World

Module 1 | Transitioning to the Cellular World

Lesson 1 | The Cellular World | Where it All Comes Together

As we've seen so far, with each level of scale comes a new level of complexity: from subatomic particles to atoms, from atoms to molecules, and from molecules to macromolecules. Naturally, adding another level of scale on top of this as we zoom out and look at cellular structures increases the level of complexity again.

The cellular world may look very different from what we've seen so far because as we zoom out, objects become smaller and biological processes therefore look to be more fluid. However remember that the cellular world is built from nothing more than the macromolecules that we have learned about: proteins, polysaccharides, nucleic acids, and lipids, all working together in a very mechanical way. In other words, when we look at cellular function we're really looking at the manifestation of the collection of macromolecules working together in the macromolecular world. In fact, we've already had glimpses of the cellular world when we learned about some of the mega-complexes like NPCs, focal adhesions, the flagellum, and the lamellipodium.

The cellular world is fascinating because it allows us to have a clear view of both the macromolecular level below upon which the cell is built and also to see how different cellular structures and compartments work together for the overall function of the cell.

One important point to keep in mind throughout this chapter is that although we will usually show cellular structures and macromolecules without the surrounding solution, remember that everything we see, both intracellular and extracellular,

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is surrounded by some type of aqueous solution. These solutions are formed primarily of water molecules, but also contain ions, molecules, and soluble proteins. There is no empty space inside cells except for the tiny spaces between adjacent molecules.

Lesson 2 | Mechanical Fluidity

Let's take a moment to orient ourselves as we change scales to transition to the cellular world. So far we've been measuring the molecular and macromolecular worlds in nanometers (nm). For example, a molecule of glucose is about 1 nm wide, ATP synthase is about 10 nm wide, and the NPC is about 100 nm wide. We're going to now transition into the micrometer (μm) world where 1 μm equals 1000 nm, which is approximately 10 NPCs side by side. Cells vary widely in size but on average range from about 10 - 40 μm in diameter. In fact, some very large cells are a few hundred μm in diameter and can even be seen by the naked eye.

It's important to understand that although the cellular world is much larger than the molecular and macromolecular worlds, the physics of how objects in this world behave are still very different than what we experience in our everyday world. For example, we might expect the water molecules in our cup of coffee to behave similarly to water molecules in a swimming pool. Although a cup of coffee is much smaller than a swimming pool, it's still large enough to accommodate 300 million water molecules in diameter, more than enough to allow water to continue behaving like the liquid we know it to be. We can create water waves in a cup of coffee just like we can in a swimming pool.

However look at the edge where the coffee meets the cup and you'll notice something interesting. This meniscus, which we discussed earlier, results from water tension between the water molecules and the coffee mug. When looking at a meniscus, a water strider, or a tiny fly caught inside a water droplet, it's clear that at this millimeter scale water behaves very differently. It also appears to be more viscous. In fact, the diameter of an average cell is only about 10,000 water molecules in diameter. At this tiny scale water behaves much differently than what we would expect to see even at the millimeter scale.

The take home message here is that in the cellular world water is still a fluid, but it behaves much more mechanically than we would expect given what we're used to seeing in our everyday world. This is because unlike in a cup of coffee or swimming pool, the size of the individual water molecule in a cell is not negligible.

Lesson 3 | DNA, The Puppet master

We've learned that cells are a collection of macromolecules working together however cells are more than just the sum of their parts. Cells are entities of their own and need to be understood as such. The reason we say that cells are the fundamental unit of life is because cells are alive and macromolecules are not. Somehow, these macromolecules must work together for a common function: life.

Even if we look at some of the most simplest life forms on the planet, single-celled organisms, it’s clear by the way these little creatures behave that they are indeed alive. What is the physical source of this life? If we look closer, we can at least see the source of their behaviour which is the collection of all of the physical macromolecular components working together, the vast majority of which are proteins. In other words, proteins are the eyes, ears, arms, and legs of a cell, which is why we've been spending so much time learning about them.

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But proteins come and go. They are built, degraded and recycled, and the prevalence of each protein dynamically changes as the needs of the cell change. Lipids and carbohydrates also undergo turnover. There's something more permanent than proteins and that is the blueprints that code for them, DNA. The information coded in DNA is the foundation upon which the entire cell is built. DNA includes not only the codes to build every protein in the cell but also the codes that regulate when these machines should be built, how many should be made, and so on. The incredible physical components that we see when we look at a cell are simply manifestations of the DNA code. In other words, proteins are puppets and DNA is the puppet master.

In fact, when looked at in this way, life is simply a DNA code. DNA is abstract and can't actually do anything so we only get a glimpse of what the code means when we see it through the proteins and the resulting cell that DNA builds around itself. A good analogy would be computer code. The computer code is like DNA whereas the program or game is the manifestation of the code, just like proteins and the rest of the cell components are manifestations of the DNA code.

Lesson 4 | But Proteins Pull the Strings

Was the last lesson convincing? What if we told you that proteins regulate their own production by regulating DNA, fix mistakes in the DNA code, and replicate all of the DNA macromolecules when it comes time for the cell to divide? In fact, the protein DNA polymerase actually replicates its own DNA code. When trying to determine who works for who, we can just as easily turn the tables around on the so-called puppet master.

For example, what if the DNA code was simply a library that was built and continues to be maintained by all of the proteins in the cell? After all, it would be prudent for each protein to keep a permanent copy of itself in a safe location. If this was the case, all of the proteins would work very hard to protect it, and would probably keep it in a centralized location where it would be safe.

The truth is that this is a problem of the chicken and the egg and no one actually knows the right answer. Proteins are the machines but DNA is the instructions. It's hard to say which came first, but mother nature has provided us with a tantalizing clue: a macromolecule that can both act as instructional code like DNA but is also capable of folding into three dimensional shapes like a machine. Can you guess what this might be?

We'll discuss this topic in more detail when we learn about evolution in a later unit but for now try to keep this concept in mind as we continue through the rest of the chapter.

Lesson 5 | Prokaryotes and Eukaryotes

There are two types of organisms that exist on Earth: prokaryotes and eukaryotes. Prokaryotes are composed of prokaryotic cells. They are single-celled organisms such as bacteria that contain a plasma membrane around the cell but no intracellular membrane-enclosed compartments. Prokaryotes therefore do not possess a cell nucleus and their DNA is thus in the same aqueous solution as all of the other cellular components. Generally speaking, prokaryotic cells are smaller and less complex than eukaryotic cells.

Eukaryotes are composed of eukaryotic cells. Eukaryotes include all multicellular life such as plants, animals, insects, and fungi, as well as protists which are eukaryotic single-celled organisms. Examples of protists include yeast, paramecia, and many other very interesting-looking creatures. Diatoms for instance, which comprise almost half of the mass of all organic

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life in the oceans, live within a house of glass! Eukaryotic cells possess plasma membrane-enclosed intracellular compartments such as nuclei that compartmentalize different cellular structures and functions. These intracellular compartments are called organelles. Eukaryotic cells are usually also larger and more complex than prokaryotic cells.

Although they’re more complex, we’re going to focus on eukaryotic cells for the remainder of this chapter because they contain many great examples of how macromolecular structures can directly affect the shape and function of cells and organelles. These examples will show that the structure/function relationship applies not only to structures of the same scale but also transcends between the different worlds that we’ve learned about.

For example, in the disease sickle cell anemia, a single molecular change leads to major changes in macromolecular structures which in turn alters the structure of red blood cells. The misshapen red blood cells in turn affect the entire organism.

Module 2 | Machines do All the Work so Cells Produce Machines

Lesson 1 | Where to Begin

The downtown area in a city is usually located in the city center. It's the busiest and arguably the most important area in any city. A large fraction of the traffic moving throughout the city moves to and from downtown.

When you look at a eukaryotic cell, what's the largest, most prominent structure that first grabs your attention? Probably the sphere in the middle, which is called the nucleus. Let's cut away part of the cell so we can see inside.

Notice the smaller sphere in the center of the nucleus. This structure is called the nucleolus. Although all parts of a cell are important and necessary for proper cellular function, we'll soon learn why the nucleolus is fundamental to all cellular functions. The nucleolus is located in the center of the cell just like downtown is located in the center of the city. For this reason, we’re going to start our journey at the nucleolus and work our way outwards.

In the previous chapters we worked our way from simple to complex as we progressed upwards through the subatomic, atomic, molecular, and macromolecular worlds. In this chapter we’re going to start with a very fundamental cellular concept that starts deep inside the nucleolus of every eukaryotic cell. From there we’ll work our way outwards which as we’ll see, naturally builds on this fundamental concept both structurally and functionally because every part of a cell is connected.

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Lesson 2 | The Nucleolus | A Factory for Making Ribosomes, the Protein-Building Machines

We're going to start our journey with one simple section of DNA buried deep in the middle of the nucleolus of a eukaryotic cell. Everything that we will learn about the cell can lead back to this one simple point at the very center. To be precise, the interaction between valence shell electrons at the subatomic level within this DNA macromolecule that are responsible for the positioning of atoms in 3D space and each covalent bond holding this molecule together.

There's something special about this specific sequence of nucleotides within this DNA macromolecule. Its 3D spatial arrangement has a high affinity for the enzyme RNA polymerase. Through conformational changes, RNA polymerase pulls apart the hydrogen bonds holding the two DNA strands together, feels the specific nitrogenous bases on one of the strands through complementary interaction of hydrogen bonds and positive and negative charges, and polymerizes an RNA copy of this DNA sequence. The process of creating an RNA copy of a DNA sequence is called transcription.

As the RNA transcript is being transcribed, proteins interact with the RNA molecule. Complicated protein/RNA interactions eventually result in the formation of two protein/RNA complexes that are exported to the cytosol through the nuclear pore complex (or, NPC). The RNA macromolecules in these complexes behave like molecular machines rather than temporary information storage devices.

This cell has just created a protein-making machine called a ribosome and the nucleolus can therefore be thought of as a ribosome-producing factory. Because proteins do everything and ribosomes produce proteins, a factory that produces and assembles ribosomal subunits can be thought of as one of the most important parts of a cell.

Lesson 3 | The Nucleolus is Dynamic

As we continue our journey through the cellular world remember that everything we learn about is dynamic, meaning continually changing. Do you exist as a static organism? Of course not. You move around, your body changes, your life changes, because everything in life is dynamic.

The same is true for cells and especially for the nucleolus. First of all, the nucleolus only exists as a discrete part of the cell because of dynamic interactions between specific DNA sequences and the enzyme RNA polymerase. If we could hypothetically hide the DNA sequence in the center of the nucleolus thereby preventing the recruitment of RNA polymerase, no RNA transcript would be produced. This would mean that no other proteins would be recruited to the transcript and the entire nucleolus would rapidly disassemble.

Nucleolar activity is actually regulated depending on the cell's need for new ribosomes. In fact, 70% of all proteins found in the nucleolus are not involved in ribosome production. They are instead thought to regulate nucleolar activity by shuttling to or receiving information from other parts of the cell. For example, cells that undergo a lot of growth exhibit large nucleoli to keep up with the increased demand for protein production.

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Lesson 4 | The Nucleus | A Library of Information and Instructions

Unlike nucleolar DNA, the function of the vast majority of the rest of the DNA in the nucleus is to store the blueprints for all of the proteins within the cell as well as to store instructions on how these blueprints should be used. All of this information is stored in the form of nucleotide sequences along the length of the linear DNA chain. This means that a permanent recipe for every protein in the cell is stored in the form of DNA, a very stable macromolecule that is kept safe and enclosed in the middle of the cell.

For protein blueprints, DNA nucleotide sequences are actually a coded form of information which stores the amino acid sequence of a protein. Because there are only four types of nucleotides but 20 types of amino acids, the code is not a one to one ratio. Instead, three adjacent nucleotides code for one amino acid. For example, the DNA nucleotide sequence TCA-GAG-AAT codes for the amino acid chain serine-glutamate-asparagine. Proteins are on average about 300-400 residues long so the amount of DNA needed to code for an average protein is about 1000 nucleotides. DNA sequences that code for proteins are called genes and the DNA sequences in between the genes act as instructions that regulate when each gene is used.

To go from DNA code to protein, an RNA transcript of the gene is produced and exported to the cytosol. Cytosolic ribosomes then translate the RNA nucleotide sequence into an amino acid sequence as they polymerize the polypeptide chain.

The transcription of RNA from DNA followed by the translation of RNA into protein is referred to as the central dogma of biology. All proteins in all cells are made this way, even the proteins that are part of the ribosome itself. How are ribosomal proteins made from ribosomes? We'll answer that question when we learn about evolution in a later unit.

Lesson 5 | The Nucleus is Dynamic

The nucleus is a master control center. Master plans are stored, orders are given, and changes are made in response to signals coming from outside the nucleus and even outside the cell. Therefore in much the same way that the nucleolus is dynamic, the nucleus is also very dynamic. Cells don't produce all proteins at the same time. Different proteins are required at different times and in varying amounts during the life cycle of a cell. Maintaining just the right amount of each protein is crucial for proper cell function.

Most proteins undergo turnover like a commodity. Just as ribosomes are producing them, large protein complexes called proteasomes are breaking them down into amino acid subunits. The amount of each protein that's present in a cell will therefore depend on the rate of transcription, translation, and break down. Of these three, transcription is the most important because it's the starting point in the life cycle of a protein.

One of the most basic ways in which transcription is regulated is by exposing or concealing genes. As you may have guessed, this is performed by protein machines. In fact, DNA is usually found in complex with regulatory proteins. This protein/DNA complex is called chromatin and one entire chromatin fiber, which comprises a single, long DNA chain, is called a chromosome. Most eukaryotic cells possess multiple chromosomes. Through conformational changes, these regulatory proteins can change the packing arrangement of chromosomes to fine tune which genes are exposed and which are concealed.

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Lesson 6 | Proteins are Required Everywhere

Proper cellular function requires different proteins working all over the cell. In terms of physical space, there are three areas within a cell: The aqueous solution inside the cell which includes the cytosol and the nuclear solution (referred to as the nucleoplasm), the aqueous solution within the different intracellular compartments, and the hydrophobic plasma membranes that separate these hydrophilic solutions from each other.

Although the translocation of proteins and other macromolecules across the NPC is regulated, the cytosolic and nucleoplasmic aqueous solutions, which include all ions and small molecules, are continuous with each other. Therefore although protein composition differs between cytosol and nucleoplasm, the baseline solution such as pH, ion concentration, and small molecule concentration between these two compartments is the same. On the contrary, the aqueous solutions within other intracellular compartments, which are referred to as organelles, are completely separated from the cytosolic and nucleoplasmic solutions. The ionic, molecular, and protein composition inside organelles is thus different than the solution outside these organelles.

Different proteins are required in all of these areas, including the hydrophobic membranes that separate them. These so-called membrane proteins are embedded in the plasma membrane via hydrophobic residues exposed on the outside of the protein.

Proteins that are required in the cytosol are simply translated by cytosolic ribosomes. Proteins required in organelles or in plasma membranes are also translated by ribosomes, however during translation the first few amino acids that are produced act as a signal sequence that binds to the large structure that we see adjacent to the nucleus: the endoplasmic reticulum (or ER). Proteins are then translated directly into the ER or into the ER membrane. When many ribosomes are translating proteins into the ER, the surface of the ER looks rough because all of the ribosomes look like bumps. This type of ER is therefore referred to as the rough ER (or RER).

Lesson 7 | The Protein Manufacturing Facility | RER

The RER and Golgi apparatus together represent a huge protein manufacturing, modifying, and sorting system for producing and distributing proteins to all organelles and membranes within the cell. Examples of cellular destinations for these proteins include lysosomes, vesicles, the extracellular solution, vacuoles, the cell membrane, organellar membranes, the nuclear envelope, mitochondria, chloroplasts, as well as resident RER and Golgi proteins required here to work at the assembly plant.

The RER is composed of many interconnected irregularly-shaped membrane-enclosed sacs called cisternae which are continuous with the outer nuclear envelope. The volume inside these cisternae, referred to as the RER lumen, is small allowing for a high surface area to volume ratio. Although usually depicted as static, the RER is highly dynamic, changing shape and size to accommodate cell needs.

Proteins that enter the ER are chemically modified to prepare them for the environment that they will encounter when they reach their destination. Two common types of modification are disulfide bond formation and glycosylation. Remember that we learned about disulfide bonds in a previous chapter. Glycosylation refers to the covalent attachment of carbohydrate molecules, in this case, to a protein. Both disulfide bond formation and glycosylation are carried out by resident RER enzymes.

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Lesson 8 | The Protein Manufacturing Facility | The Golgi

Through budding and fusing of small membrane-enclosed spherical containers called vesicles, proteins travel from the RER to the Golgi, and then successively through each of the Golgi cisternae. Each membrane budding and fusion event is coordinated by many proteins. We saw an example of vesicle budding when we learned about the protein COPII in a previous chapter.

Throughout the Golgi cisternae proteins are further chemically modified by enzymes and sorted based on their intended destination. From the final cisternae, vesicles bud off and travel to their destination, which may include for example, vacuoles, lysosomes, the plasma membrane, or the extracellular environment.

These vesicles contain soluble proteins in the aqueous solution inside as well as proteins in the vesicle membrane that will be transferred to the membrane of the target organelle or cell membrane. Examples of membrane proteins include the sodium/potassium pump and the calcium pump that we learned about earlier, both of which function in the cell membrane.

There are still many more cellular structures that we need to learn about, many of them very important for cellular function. However it's worth taking a brief pause to look at the nucleolus, nucleus, RER, Golgi, and ribosomes, which collectively are the most prominent structures in most cells, as a huge manufacturing plant with one goal: synthesize all cell machinery and deliver these machines to their proper destination. Think of this manufacturing plant as the functional backbone of the cell.

Module 3 | Other Cellular Components

Lesson 1 | Smooth Endoplasmic Reticulum (SER)

The smooth ER (or SER) is an interconnected system of tubule-like membranous structures that is continuous with the RER. One of the main functions of the SER is to synthesize new lipids for incorporation into all of the various membranes throughout the cell, however the SER also has several other functions that depend on cell type. For example, in human liver cells the SER is a very prominent organelle that contains detoxifying enzymes. In muscle cells the SER forms a specialized organelle called the sarcoplasmic reticulum which controls the release of Ca2+ ions into the cytoplasm to initiate muscle contraction.

The difference between the RER and SER is therefore as follows: The RER modifies, sorts, and traffics proteins in conjunction with the Golgi and thereby serves as the main protein manufacturing facility in the cell. The SER on the other hand produces the lipids for membranes and serves as the production site for any specialized products that need to be produced. These specialized products will depend on the cell type.

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Lesson 2 | Lysosomes

Lysosomes act as the cell's recycling bins by breaking down organic macromolecules into their monomer building blocks. These macromolecules include the food that unicellular organisms ingest during phagocytosis as well as intracellular components that are damaged or obsolete and thus no longer required by the cell. Even entire organelles like mitochondria and chloroplasts are digested by lysosomes when they are no longer needed.

Lysosomes are spherical membrane-enclosed organelles that contain a unique set of soluble digestive proteins in their lumen and a unique set of receptor proteins in their membrane. The pH in the lysosomal lumen is between 4.5 to 5.0, which is very acidic compared to the cytosol pH which is around 7.2. This is because the hydrolytic enzymes that function within lysosomes function optimally at a low pH. This ensures that if these hydrolytic enzymes were to be accidently released into the cytosol, they wouldn't cause widespread damage to the cell. The high acidity in the lysosomal lumen is maintained by proton pumps that pump protons from the cytosol into the lysosome.

Lysosomal enzymes are produced in the RER and travel through the RER/Golgi trafficking system where they are contained within budding vesicles, many of which fuse together to form the lysosome.

Lesson 3 | Vacuoles

Vacuoles are mainly found in plant cells but are also present in some animal cells, bacterial cells, and protists, which are single-celled eukaryotes. Vacuoles are very large organelles, occupying approximately 30-70% of the cell volume, and they have a variety of functions depending on the organism.

In plant cells vacuoles provide turgor pressure to the cell. The positive pressure in vacuoles generated by osmosis pushes outward where it is balanced by the tension provided by the cell wall. Plant cells are therefore very stiff when they are healthy and full of water.

Plant vacuoles can also store nutrients or collect waste depending on the organism. Other molecules stored in vacuoles include poisons that protect the plant against plant-eating animals. For example tobacco plant vacuoles store nicotine while coffee and tea plant vacuoles store caffeine. Vacuoles in flower petals contain colored pigments that attract pollinating insects. In this way, vacuoles have something in common with the SER in that both organelles are highly specialized for either producing or storing molecules according to the specific requirements of the cell.

In protists the vacuole acts as a contractile pump that pumps out excess water that flows into the cell.

Lesson 4 | Mitochondria and Chloroplasts

Mitochondria are organelles that convert the chemical energy stored in glucose to a much easier to use form of chemical energy stored in molecules of ATP. They are thought to have once been separate organisms because they possess their own DNA, their own ribosomes, and they divide like bacteria by binary fission. Mitochondria possess two plasma membranes. Their inner membrane is thought to have been the original membrane while their outer membrane was most likely derived from the host cell that originally engulfed the mitochondria. The solution between the inner and outer

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membranes is called the inter-membrane space while the solution contained within the inner membrane is referred to as the matrix.

Chloroplasts are also thought to have once been a separate organism for the same reasons as mentioned for mitochondria. Chloroplasts convert sunlight energy into chemical energy which is then stored within glucose molecules. Unlike mitochondria, chloroplasts possess three membranes: An outer membrane, an inner membrane, and a thylakoid membrane. The solution between the inner membrane and the thylakoid membrane is called the stroma and is analogous to the mitochondrial matrix. The solution inside the thylakoid membrane is referred to as the thylakoid lumen.

We will learn more about mitochondria and chloroplasts in the next unit when we learn about how cells obtain and use energy.

Lesson 5 | Cytoskeleton

In the previous chapter we learned about the three proteins that form the cytoskeleton: F-actin, microtubules, and intermediate filaments. Together, these three filamentous proteins provide shape, mechanical support, and transportation roadways throughout the cell. However because plant cells are immotile they possess a stiff cell wall that provides most of their mechanical support.

For most cells F-actin filaments provide shape to the cell membrane just like we saw earlier for the lamellipodium and filipodia in migrating fibroblasts. However they can also take on specialized roles such as contraction in muscle cells. Muscle cells are specialized cells that are stuffed full of actin and myosin filaments, which is why we say that meat has a lot of protein.

Microtubules polymerize outwards in all directions starting from the microtubule-organizing center (or MTOC) located near the middle of the cell, just outside the nucleus. Microtubules position the various organelles throughout the cell by interacting with motor proteins that are attached to the organellar membranes. During cellular division, microtubules also pull apart the DNA chromosomes, dividing them evenly between the two new cells. In nerve cells, microtubules act as roadways upon which motor proteins transport neurotransmitters from the cell body to the axon terminal where they are needed for signaling. Microtubules also form the cilia that line our lungs.

Lesson 6 | Cytosol

Although we normally show the cytosol as empty so as not to distract from the organelles that we're learning about, the cytosol is a very crowded environment filled with ions, molecules, and proteins. In fact proteins occupy about 20-30% of the cytosolic volume. We can't say what the function of the cytosol is because there are so many processes that take place in the cytosol such as signal transduction, metabolic processes, protein synthesis by ribosomes, and cargo transport by motor proteins on microtubules. In prokaryotes, nearly all cellular processes occur in the cytosol because prokaryotes do not possess organelles.

The concentration of ions and molecules in the cytosol is highly regulated. Cytosolic pH is also highly regulated since most proteins that function in the cytosol function optimally at a pH of 7.2. Given the huge volume and many proteins that function in the cytosol, it's crucial for the cell to maintain the cytosolic pH at 7.2. One of the ways this can be achieved is by proton pumps on the cell membrane.

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Lesson 7 | The Cell Membrane

The cell membrane is composed of a very thin lipid bilayer. This bilayer consists of two layers of amphipathic phospholipid molecules whose hydrophobic tails face each other while their hydrophobic heads face outwards, towards the cytosol or extracellular solution. The cell membrane thus acts as a hydrophobic barrier that surrounds the cell.

It's interesting to note that spherical membranes can form spontaneously from phospholipids in vitro. This suggests that the shape of the cell membrane is at least partially maintained by the phospholipids themselves however we do know that membrane proteins also play a role in maintaining the shape not only of the cell membrane, but also of all organellar membranes within the cell.

The main function of the cell membrane is to separate all of the intracellular contents from the extracellular environment. This separation protects the cell from its environment and ensures that the presence and concentration of ions, molecules, and proteins is maintained.

If the cell membrane were composed only of phospholipids, it would be impenetrable to all hydrophilic molecules, allowing only small hydrophobic molecules to pass. However cells need to communicate with their environment to obtain food and other important molecules as well as to excrete waste, so the cell membrane is embedded with many proteins that selectively allow some molecules to pass but not others. In this way, the plasma membrane is semi-permeable. For example, something as simple as water transport across the membrane requires specialized water channels called aquaporins which are embedded throughout most cell membranes.

The cell membrane is filled with all sorts of proteins involved in many functions including ion and molecule transport, enzymatic activity, and cell signaling pathways. Some proteins also act as attachment sites that anchor the cytoskeleton to the cell membrane. Moreover, the cell membrane behaves like a two dimensional fluid as phospholipids and proteins diffuse through the bilayer.

Lesson 8 | The Cell Wall

Plant cells, algae cells, fungi cells, and most prokaryotic cells possess cell walls around their cell membrane. Cell walls are made of cellulose which are polymers of glucose and are usually stiff and rigid. Cell walls not only provide mechanical support for the cell but also maintain cell shape, provide protection, act as molecular filters, and restrict osmosis-induced water absorption thereby preventing bursting.

In multicellular organisms with cell walls such as plants, the cell walls between adjacent cells attach to each other. This creates a network of cellulose fibers that connect all cells together and provide shape to the organism as a whole. When the plant dies and the cells degrade, the network of cellulose remains as what we call wood.

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Module 4 | Incredible Diversity

Lesson 1 | The Many Types of Cells

As we all know, there is an incredible amount of variation between the different organisms that exist on this planet and an equally incredible amount of variation between the different types of cells that we see. We already know that we can divide organisms and their cells into two categories, prokaryotes and eukaryotes. However each of these categories can also be further subdivided.

Prokaryotes can be divided into bacteria or archaea whereas eukaryotes can be divided into protists (which are single-celled eukaryotes), plants, fungi, and animals. We can all see the diversity between organisms in our everyday lives but there's just as much diversity in the single-celled world as well, even amongst prokaryotes. Although prokaryotic cells are approximately 10 times smaller than eukaryotic cells, they still exhibit a wide variety of shapes such as spherical, lumpy, rectangular, and rod-like. Many prokaryotes have flagella that propel them through their environment. The bacteria Thiomargarita namibiensis, the largest bacterium ever discovered, can grow up to three quarters of a millimeter in length, which is large enough to see without using a microscope!

If we look at protists, we see an even more remarkable diversity in different life forms that exist. Although protists are just single cells, some of them look and behave like multicellular organisms.

Lesson 2 | Multicellular Organisms

We can write an entire textbook just on multicellular organisms and the diversity we see between them however for this lesson let's focus on just a few important concepts.

First, because multicellular organisms are made from nothing more than a collection of cells, they are simply elaborate manifestations of the cells themselves. For example, when we see a unicellular protist ingesting a bacterium or a shark eating a fish, we're actually looking at the same thing. The unicellular protist possesses membrane extensions called cilia which propel it through its environment, proteins in its cell membrane that detect the chemical signals of the bacterium, and a membrane invagination that traps bacteria and pulls them into a lysosome. In the multicellular shark, these same functions occur in different specialized cells of the shark's body rather than different specialized structures within a single cell, forming a tail and fins, eyes and nose, and a mouth with sharp teeth respectively. The fish will end up in the shark's stomach, a highly acidic environment where organic matter is chemically broken down by enzymes, whereas the bacteria will end up in the lysosome of the protist, which is also a highly acidic environment where organic matter is chemically broken down by enzymes.

The second important concept is that in multicellular organisms the organism as a whole is the individual, not the individual cells themselves. As humans, we shed our skin cells often. When we get cut, blood cells leave our body. And during embryonic development the cells between our fingers actually kill themselves so that our fingers can separate from each other and move independently. The DNA inside each of our cells is programmed to know that it is just part of a bigger picture and that the survival of a single cell is irrelevant. Sometimes through DNA mutations, cells forget this, which may lead to cancer.

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Lesson 3 | Summary | From Protons to Cells

Everything is interconnected. Electrons, protons, and neutrons come together in different combination to form atoms. Atoms then covalently join with other atoms via the sharing of their valence shell electrons to form functional groups which in turn come together to form molecules. There are four categories of biological molecules that either function in monomer form or are polymerized into macromolecules, the building blocks of cells.

At some point along this line cells become alive. When looking at single cells move through their environment it's hard to believe that they're composed of nothing more than mechanical, machine-like macromolecules. Their movement is so graceful and coordinated that it's hard to fathom the complexity of the dynamic interplay between all of the macromolecules within the cell.

Throughout this unit we've learned about the physical components that cells are built from. In the next unit we'll learn how cells use energy obtained from their environment to power their many molecular machines. In essence, we'll learn how the protist obtains energy from the bacterium it ingested and then how it uses that energy to move through its environment to capture and eat more bacteria.