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The Cell

The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life, and all living things are composed of cells. Most animal cells are between 0.2 and 8 ?m in diameter and between 0.01 and 1 ?m in thickness, while plant cells are between 0.2 and 200 ?m in diameter and 1 and 10 ?m in thickness. The cell is the fundamental unit of life. All living organisms are composed of trillions of cells, each with a unique set of DNA instructions. A single human cell may have an estimated 50,000 genes, and all cells contain the same basic components: a plasma membrane, a cell nucleus, and a cytoplasm, which contains various organelles. All cells are derived from pre-existing cells, through cell division. The cell was discovered by Robert Hooke in 1665, although others had previously described the components of cells, such as Antonie van Leeuwenhoek who is credited with the discovery of red blood cells. The term cell comes from the Latin word cella, meaning "small room", because of its small size within the body. The smallest unit of a cell is called a granule, which is a spherical particle of RNA or DNA. The cell is composed of a cytoplasm enclosed by a cell membrane, which contains a semi-permeable lipid bilayer called a plasma membrane. The plasma membrane is a phospholipid bi-layer which acts as a barrier for controlling what materials can enter and leave the cell. The nucleus is a membrane-bound organelle inside the cell, in which the cell's DNA is housed. The nucleus is separated from the cytoplasm by a nuclear envelope. The DNA is tightly coiled with many strands of DNA tightly coiled around each other. The nucleus is the command center of the cell, controlling the cell cycle, gene expression, cell division and protein synthesis. The cytoplasm is a fluid compartment of the cell, which contains the cell organelles. The cytoplasm is usually separated from the cell membrane by a cell membrane. The organelles are made of different materials and are involved in many different cellular functions. The organelles are the following: the Golgi apparatus, the endoplasmic reticulum, the ribosomes, the lysosomes, the peroxisomes, the mitochondria and the vacuoles. The organelles are used for housekeeping functions and they also help with the cell's function. The cell cycle is a sequence of events that a cell goes through as it divides. The cell cycle is divided into four different phases: the G1 phase, S phase, the G2 phase and the M phase. There are four main stages in the cell cycle, G1, S, G2 and M. The cell cycle is also called the eukaryotic cell cycle, because humans and other eukaryotes have cell cycles. The cell cycle is regulated by the cell cycle checkpoints. The cell cycle checkpoints are the following: the G1/S checkpoint, the G2/M checkpoint and the mitotic entry checkpoint. The G1/S checkpoint is the first checkpoint, which controls when a cell enters the G1 phase of the cell cycle. The G2/M checkpoint controls when the cell enters the M phase of the cell cycle. The mitotic entry checkpoint controls when a cell enters mitosis.

Prokaryotic vs. Eukaryotic Features

302 Practice Problems
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00:47
Physical Biology of the Cell

(a) Calculate the average volume and surface area of mitochondria in yeast based on the confocal microscopy image of Figure $2.18(\mathrm{C})$
(b) Estimate the area of the endoplasmic reticulum when it is in reticular form using a model for its structure of interpenetrating cylinders of diameter $d \approx 10 \mathrm{nm}$ separated by a distance $a \approx 60 \mathrm{nm},$ as shown in Figure 2.25

What and Where: Construction Plans for Cells and Organisms
Sana Riaz
04:36
Essential Cell Biology

There are three major classes of protein filaments that make up the cytoskeleton of a typical animal cell. What are they, and what are the differences in their functions? Which cytoskeletal filaments would be most plentiful in a muscle cell or in an epidermal cell making up the outer layer of the skin? Explain your answers.

Cells: The Fundamental Units of Life
Yifan Zhou
02:22
Essential Cell Biology

Suggest a reason why it would be advantageous for eukaryotic cells to evolve elaborate internal membrane systems that allow them to import substances from the outside, as shown in Figure $1-25$

Cells: The Fundamental Units of Life
Yifan Zhou

The Nucleus

295 Practice Problems
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06:44
Molecular Cell Biology

What types of experimental strategies do researchers employ to study cell cycle progression? How do genetic and biochemical approaches to this topic differ?

The Eukaryotic Cell Cycle
Billy Laise
02:45
Molecular Cell Biology

Describe the ways in which each of the following pathogens can disarm their host's immune system or manipulate it to their own advantage:
a. Pathogenic strains of Staphylococcus
b. Enveloped viruses

Immunology
00:34
Molecular Cell Biology

In $1997,$ Dolly the sheep was cloned by a technique called somatic-cell nuclear transfer (or nuclear-transfer cloning). A nucleus from an adult mammary cell was transferred into an egg from which the nucleus had been removed. The egg was allowed to divide several times in culture, then the embryo was transferred to a surrogate mother who gave birth to Dolly. Dolly died in 2003 after mating and giving birth herself to viable offspring. What does the creation of Dolly tell us about the potential of nuclear material derived from a fully differentiated adult cell? Does the creation of Dolly tell us anything about the potential of an intact, fully differentiated adult cell?

Stem Cells, Cell Asymmetry, and Cell Death
Sam Limsuwannarot

Ribosomes

44 Practice Problems
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0:00
Physical Biology of the Cell

RNA polymerase and ribosomes
(a) If RNA polymerase subunits $\beta$ and $\beta^{\prime}$ together constitute approximately $0.5 \%$ of the total mass of protein in an $E .$ coli cell, how many RNA polymerase molecules are there per cell, assuming each $\beta$ and $\beta^{\prime}$ subunit within the cell is found in a complete RNA polymerase molecule? The subunits have a mass of 150 kDa each. (Adapted from Problem 4.1 of Schleif, $1993 .$
(b) Rifampin is an antibiotic used to treat Mycobacterium infections such as tuberculosis. It inhibits the initiation of transcription, but not the elongation of RNA transcripts. The time evolution of an $E .$ coli ribosomal RNA (rRNA) operon after addition of rifampin is shown in Figures $3.36(\mathrm{A})-(\mathrm{C})$ An operon is a collection of genes transcribed as a single unit. Use the figure to estimate the rate of transcript elongation. Use the beginning of the "Christmas-tree" morphology on the left of Figure $3.36(\mathrm{A})$ as the starting point for transcription.
(c) Using the calculated elongation rate, estimate the frequency of initiation off of the rRNA operon. These genes are among the most transcribed in $E .$ coli.
(d) As we saw in the chapter, a typical $E$. coli cell with a division time of 3000 s contains roughly 20,000 ribosomes. Assuming there is no ribosome degradation, how many RNA polymerase molecules must be synthesizing rRNA at any instant? What percentage of the RNA polymerase molecules in $E .$ coli are involved in transcribing rRNA genes?

When: Stopwatches at Many Scales
01:15
Essential Cell Biology

Which of the following statements are correct? Explain your answers.
A. An individual ribosome can make only one type of protein.
B. All mRNAs fold into particular three-dimensional structures that are required for their translation.
C. The large and small subunits of an individual ribosome always stay together and never exchange partners.
D. Ribosomes are cytoplasmic organelles that are encapsulated by a single membrane.
E. Because the two strands of DNA are complementary, the mRNA of a given gene can be synthesized using either strand as a template.
F. An mRNA may contain the sequence ATTGACCCCGGTCAA.
G. The amount of a protein present in a cell depends on its rate of synthesis, its catalytic activity, and its rate of degradation.

From DNA to Protein: How Cells Read the Genome
Eleanor Behling
03:20
Molecular Biology of the Cell

The KDEL receptor must shuttle back and forth between the ER and the Golgi apparatus to accomplish its task of ensuring that soluble ER proteins are retained in the ER lumen. In which compartment does the KDEL receptor bind its ligands more tightly? In which compartment does it bind its ligands more weakly? What is thought to be the basis for its different binding affinities in the two compartments? If you were designing the system, in which compartment would you have the highest concentration of KDEL receptor? Would you predict that the KDEL receptor, which is a transmembrane protein, would itself possess an ER retrieval signal?

Intracellular Membrane Traffic
Joanna Quigley

The Endomembrane System

82 Practice Problems
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00:54
Molecular Cell Biology

Sorting signals that cause retrograde transport of a protein in the secretory pathway are sometimes known as retrieval sequences. List the two known examples of retrieval sequences for soluble and membrane proteins of the ER. How does the presence of a retrieval sequence on a soluble ER protein result in its retrieval from the cis -Golgi complex? Describe how the concept of a retrieval sequence is essential to the cisternal-maturation model.

Vesicular Traffic, Secretion, and Endocytosis
Sam Limsuwannarot
01:19
Molecular Cell Biology

Explain why the coupled reaction $\mathrm{ATP} \rightarrow \mathrm{ADP}+\mathrm{P}_{\mathrm{i}}$ in the P-class ion pump mechanism does not involve direct hydrolysis of the phosphoanhydride bond.

Transmembrane Transport of lons and Small Molecules
Aditya Sood
06:03
Molecular Cell Biology

The proton-motive force is essential for both mitochondrial and chloroplast function. What produces the protonmotive force, and what is its relationship to ATP? The compound 2,4 -dinitrophenol (DNP), which was used in diet pills in the 1930 s but later shown to have dangerous side effects, allows protons to diffuse across membranes. Why is it dangerous to consume DNP?

Cellular Energetics
Dennis Howard

Mitochondria and Chloroplasts

97 Practice Problems
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00:52
Essential Cell Biology

In an insightful experiment performed in the 1960 s, chloroplasts were first soaked in an acidic solution at $\mathrm{pH} 4$ so that the stroma and thylakoid space became acidified (Figure $Q 14-17$ ). They were then transferred to a basic solution $(\mathrm{pH} 8) .$ This quickly increased the pH of the stroma to $8,$ while the thylakoid space temporarily remained at $p H$ 4. A burst of ATP synthesis was observed, and the pH difference between the thylakoid and the stroma then disappeared.
A. Explain why these conditions lead to ATP synthesis.
B. Is light needed for the experiment to work?
C. What would happen if the solutions were switched, so that the first incubation is in the $\mathrm{pH} 8$ solution and the second one in the pH 4 solution?
D. Does the experiment support or question the chemiosmotic model? Explain your answers.

Energy Generation in Mitochondria and Chloroplasts
00:21
Essential Cell Biology

In the following statement, choose the correct one of the alternatives in italics and justify your answers. "If no $\mathrm{O}_{2}$ is available, all components of the mitochondrial electrontransport chain will accumulate in their reduced/oxidized form. If $\mathrm{O}_{2}$ is suddenly added again, the electron carriers in cytochrome $c$ oxidase will become reduced/oxidized before/after those in NADH dehydrogenase."

Energy Generation in Mitochondria and Chloroplasts
05:57
Molecular Cell Biology

The electron-transport chain consists of a number of multiprotein complexes, which work in conjunction to pass electrons from an electron carrier, such as $\mathrm{NADH},$ to $\mathrm{O}_{2} .$ What is the role of these complexes in ATP synthesis? It has been demonstrated that respiration supercomplexes contain all the protein components necessary for respiration. Why is this beneficial for ATP synthesis, and what is one way that the existence of supercomplexes has been demonstrated experimentally? Coenzyme $\mathrm{Q}(\mathrm{CoQ})$ is not a protein, but a small, hydrophobic molecule. Why is it important for the functioning of the electrontransport chain that $\mathrm{CoQ}$ is a hydrophobic molecule?

Cellular Energetics
Dennis Howard

The Cytoskeleton

38 Practice Problems
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00:56
Molecular Cell Biology

Explain the concept of loss of heterozygosity (LOH). Why do most cancer cells exhibit LOH of one or more genes? How does failure of the spindle assembly checkpoint lead to loss of heterozygosity?

Cancer
Sam Limsuwannarot
00:45
Molecular Cell Biology

Because of oxygen and nutrient requirements, cells in a tissue must reside within $100 \mathrm{pm}$ of a blood vessel. Based on this information, explain why many malignant tumors often possess gain-of-function mutations in one of the following genes: $\beta F G F, T G F-\alpha,$ and $V E G F$.

Cancer
Sam Limsuwannarot
00:12
Molecular Cell Biology

Asymmetric cell division often relies on cytoskeletal elements to generate or maintain the asymmetric distribution of cellular factors. In $S .$ cerevisiae, what factor is localized to the bud by myosin motors? In Drosophila neuroblasts, what factors are localized apically by microtubules?

Stem Cells, Cell Asymmetry, and Cell Death
Sam Limsuwannarot

The Extracellular World

25 Practice Problems
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02:10
Molecular Cell Biology

Cadherins are known to mediate homophilic interactions between cells. What is a homophilic interaction, and how can it be demonstrated experimentally for E-cadherins? What component of the extracellular environment is required for the homophilic interactions mediated by cadherins, and how can this requirement be demonstrated?

Integrating Cells into Tissues
Smrithi Upadhyayula
02:07
Molecular Cell Biology

Three systems of cytoskeletal filaments exist in most eukaryotic cells. Compare them in terms of composition, function, and structure.

Cell Organization and Movement I: Microfilaments
Sara Ryan
00:59
Molecular Cell Biology

The studies of Palade and colleagues used pulse-chase labeling with radioactively labeled amino acids and autoradiography to visualize the location of newly synthesized proteins in pancreatic acinar cells. These early experiments provided invaluable information on protein synthesis and intercompartmental transport. New methods have replaced these early approaches, but two basic requirements are still necessary for any assay to study this type of protein transport. What are they, and how do recent experimental approaches meet these criteria?

Vesicular Traffic, Secretion, and Endocytosis
Sam Limsuwannarot

Membrane Composition

68 Practice Problems
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03:50
Physical Biology of the Cell

Here we consider an electrical current through a single ion channel, as shown in Figure $17.25 .$ We start by treating an ion channel as a cylindrical pore through the cell membrane. The channel is of length $L \approx 5 \mathrm{nm}$ and is filled with water. The concentration difference of $\mathrm{Na}^{+}$ ions across the channel is $\Delta c \approx 100 \mathrm{mM}$. This concentration difference produces a flux of ions through the channel given by $D \Delta c / L$ where $D$ is the diffusion constant for ions in water. For small ions, like $\mathrm{Na}^{+}$, the diffusion constant in water is of the order of $1 \mu \mathrm{m}^{2} / \mathrm{ms}$
(a) Assuming that the channel cross-section has an area $A \approx 1 \mathrm{nm}^{2},$ compute the number of sodium ions that pass through the channel every second due to diffusion.
(b) The figure shows the current recording from a single channel. Use the figure to estimate the number of ions passing through the channel per second, when it is open. How does your result compare with the result you derived in (a)?
(c) Using the figure of a single-channel current recording. estimate the probability that the channel is open. Sketch a graph of the current recording you expect to get from a channel that is open with probability $1 / 2$

Biological Electricity and the Hodgkin-Huxley Model
Sana Riaz
01:57
Physical Biology of the Cell

Show that the electrical circuit representing a patch of membrane given in Figure 17.11 can be substituted with an equivalent circuit with one effective conductance and one battery source. What are the effective conductance and voltage of these two elements in terms of the conductance and Nernst potential for $\mathrm{Na}^{+}$ and $\mathrm{K}^{+}$ ?

Biological Electricity and the Hodgkin-Huxley Model
02:11
Physical Biology of the Cell

Consider the function $h\left(x_{1}, x_{2}\right)=x_{1}^{2}+x_{1} x_{2}-2 x_{2}^{2},$ which we assume describes the shape of a deformed lipid bilayer membrane. As shown in Figure $11.14, x_{1}$ and $x_{2}$ are the coordinates of the reference plane below the membrane.
(a) Make a plot of the height as a function of $x_{1}$ and $x_{2}$
(b) Compute the principal radii of curvature as functions of
$x_{1}$ and $x_{2}$
(c) Compute the bending free energy for the piece of membrane corresponding to the square $0 \leq x_{1} \leq 1$ and $0 \leq x_{2} \leq 1$ in the reference plane.

Biological Membranes: Life in Two Dimensions
Sana Riaz

Membrane Proteins and Carbohydrates

74 Practice Problems
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03:57
Physical Biology of the Cell

In the chapter, we derived the Nernst equation (Equation 17.3 ) using the Boltzmann distribution. Derive the same result, but this time by using the fact that in equilibrium the net flux of ions across the membrane is zero. Use Equation $13.56(p .530)$ to derive the contribution of the electrical force to the overall flux and show that by balancing this flux with the diffusive contribution you recover the Nernst equation.

Biological Electricity and the Hodgkin-Huxley Model
Sana Riaz
02:11
Essential Cell Biology

Which of the three 20 -amino-acid sequences listed below in the single-letter amino acid code is the most likely candidate to form a transmembrane region ( $\alpha$ helix) of a transmembrane protein? Explain your answer.
A. I T L I Y F G N M S S V T Q T I L L I S
B. L L L I F F G V M A L V I V V I L L I A
C. L L K K F F R D M A A V H E T I L E E S

Membrane Structure
Sana Riaz
03:27
Essential Cell Biology

Consider a transmembrane protein that forms a hydrophilic pore across the plasma membrane of a eukaryotic cell. When this protein is activated by binding a specific ligand on its extracellular side it allows $\mathrm{Na}^{+}$ to enter the cell. The protein is made of five similar transmembrane subunits, each containing a membrane-spanning $\alpha$ helix with hydrophilic amino acid side chains on one surface of the helix and hydrophobic amino acid side chains on the opposite surface. Considering the function of the protein as a channel for $\mathrm{Na}^{+}$ ions to enter the cell, propose a possible arrangement of the five membrane-spanning $\alpha$ helices in the membrane.

Membrane Structure
Sana Riaz

Membranes As Cellular Traffic Control

57 Practice Problems
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00:30
Physical Biology of the Cell

In this problem, we extend the one-dimensional model of diffusion in the presence of crowding molecules to account for the difference in size between a tracer particle (considered to be present at low concentration) and the crowders. This situation is relevant for the data shown in Figure $14.24(\mathrm{A}) .$ The tracer particles are assumed to be undergoing random walk motion on the larger tracer lattice with lattice constant $b,$ while the crowders are hopping between adjacent sites of the smaller lattice, with lattice constant $a$ (see Figure 14.26 ). The two lattices are introduced to account for the difference in size between the two molecular species.
(a) Calculate the diffusion coefficient by considering the possible trajectories of the tracer particles and their probabilities. Note that the tracer can hop to an adjacent site of the tracer lattice only if there are no crowders present. Express your answer in terms of the diffusion coefficient $D_{0}$ of the tracer particles in the absence of crowders, the volume fraction of the crowders $\phi,$ and the ratio of the tracer and crowder sizes $r=b / a$
(b) Plot $\ln \left(D / D_{0}\right)$ as a function of the volume fraction for different values of $r .$ How well does this model explain the data shown in Figure $14.24(\mathrm{A}) ?$ To make this comparison, you will need to estimate the sizes of the molecules used in the experiment from their molecular masses and a typical protein density that is 1.3 times that of water. The data are provided on the book's website.

Life in Crowded and Disordered Environments
Sana Riaz
03:51
Physical Biology of the Cell

Consider a protein sphere with a radius of $1.8 \mathrm{nm},$ and charge $Q=-10 e,$ in an aqueous solution of $c_{\infty}=0.05 \mathrm{M}$ $\mathrm{NaCl}$ at $25^{\circ} \mathrm{C}$. Consider the small ions as point charges and use the linear approximation to the Poisson-Boltzmann equation.
(a) Fill in the steps leading to Equations 9.70 and $9.72,$ and derive the expression for the potential $V(r)$ of a charged sphere in a salty solution.
(b) What is the surface potential of the protein in units $k_{\mathrm{B}} T / e ?$
(c) What is the concentration of $\mathrm{Na}^{+}$ ions and of $\mathrm{Cl}^{-}$ ions at the surface of the protein?
(d) What is the concentration of $\mathrm{Na}^{+}$ and $\mathrm{Cl}^{-}$ ions at a distance of $0.3 \mathrm{nm}$ from the protein surface? (Adapted from Problem 23.2 of $\mathrm{K}$. Dill and S. Bromberg, Molecular Driving Forces, 2 nd ed. Garland Science, $2011 .$ )

Electrostatics for Salty Solutions
Sana Riaz
02:35
Essential Cell Biology

The signaling mechanisms used by a steroid-hormone-type nuclear receptor and by an ion-channel-coupled receptor are relatively simple as they have few components. Can they lead to an amplification of the initial signal, and, if $s o,$ how?

Cell Signaling
Bryan Valdivia

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