1. CELL FORM & FUNCTION Chapter 10

2. Diverse Cell Types Remember: “Form Fits Function”
The function of a cell is reflected in its shape and internal structural features.
A red blood cell (a) is shaped like a disk having an indented middle and lacks a nucleus or other organelles. This structure makes it possible for the cell to carry oxygen and fit through blood vessels that are much smaller than itself.
Liver cells (b) that synthesize proteins and glycogen look very different from muscle cells (c) that we know contract and exert force.
A neuron (d) is long and extensively branched so that it can communicate with with other cells.
Intestinal cells (e) have a large surface area to facilitate absorption.

3. Tissues and Organs
10.1 Tissues and organs are communities of cells that perform a specific function.
Cell: lowest level that can live as an organism
Tissue: a collection of cells that work together to perform a specific function.
4 main categories of tissues: epithelial, connective, muscle, nervous
Organ: two or more tissues that combine and function together
Cytoskeleton structures: determine the shape of the cell
Cell junctions: connect cells to each other and to the extracellular matrix (ECM)
ECM: a meshwork of proteins and polysaccharides outside the cell; the main part of connective tissue
The shape of cells is determined and maintained by structural protein networks in the cytoplasm, the cytoskeleton.
The structural integrity of a tissue or organ depends on:
•The ability of cells to adhere to one another, through the assembly of cytosolic proteins and other cell adhesion molecules into cellular junctions.
•The ability of cells to adhere to a meshwork of proteins and polysaccharides outside the cell called the extracellular matrix.

4. EPITHELIAL TISSUE
Functions as protection/barriers, both inside and outside of body
Formed from continuous sheets of tightly packed cells
I.e. Stratified squamous epithelium
2 or more layers, protects underlying tissues where there is abrasion
Covers outermost layer of skin, lines mouth, esophagus, vagina, anus

5. Structure and Function of Skin
The skin is a community of cells that provides a useful example for investigation of the cytoskeleton, cellular junctions, and the extracellular matrix.
Skin has two main layers:
The outer layer, the epidermis, serves as a water-resistant, protective barrier.
The layer beneath the epidermis is the dermis.
The epidermis:
is several layers thick. Cells arranged in one or more layers are called epithelial cells and together make up a type of animal tissue called epithelial tissue.
is primarily composed of epithelial cells called keratinocytes which are specialized to protect underlying tissues and organs.
also contains melanocytes which produce the pigments of skin giving it color.
Cellular junctions are present at the bottom layer of the epidermis, forming the basal lamina, which supports all epithelial cells.
The dermis layer:
is mostly made up of connective tissue, a tissue type characterized by few cells and substantial amounts of extracellular matrix
also contains nerve endings and blood vessels
is strong and flexible
the main cell type found here is fibroblasts, which synthesize the extracellular matrix and repair wounds.
Structure and Function of Skin
Epidermis: outer layer; water-resistant protective barrier; several layers thick of epithelial tissue
Melanocytes: skin color
Keratinocytes…main cells, protect underlying tissues using cytoskeletal filaments
Basal lamina…also called basement membrane; specialized form of ECM that attaches to bottom layer of keratinocytes
2 main layers: epidermis & dermis 5

6. CONNECTIVE TISSUE Connects and supports other tissues: 6 main types
Characterized by few cells suspended in extracellular matrix of fibers
The ECM might be a liquid, gel or ground solid
Types: Loose CT, Adipose Tissue, Fibrous CT, Blood, Cartilage, Bone
Loose Connective Tissue:
Attaches epithelia to underlying tissues
Holds organs in place; like “packing material”
Consists of a loose weave of 2 kinds of cells (fibroblasts & macrophages)
& 3 types of protein fibers (collaginous fibers, elastin fibers, reticular fibers)

7. DERMIS Dermis: mostly connective tissue; both loose & dense
Strong and flexible; tough protein
fibers of ECM
Blood vessels, nerves
Fibroblasts…main cells, make fibers/ECM and repair wounds

8. Cytoskeleton
10.2 Cytoskeleton: internal support for cells made up of different proteins
All eukaryotes have
microtub. and microfilaments
Only animals have
Intermediate filaments
Just as bones provide internal support for the body, the protein fibers of the cytoskeleton provide internal support for cells.
All eukaryotic cells have at least two cytoskeletal elements, microtubules and microfilaments. Animal cells also have intermediate filaments.
These elements are long chains made of protein subunits. They provide structural support and enable the movement of substances within cells.

9. Microtubules ; made of tubulin dimers Have widest diameter Centrosome
Microtubules are tubelike structures that are polymers of protein dimers. Each dimer is made of two tubulin proteins, α and β tubulin. One α tubulin and one β tubulin combine to form a tubulin dimer.
These dimers assemble to form microtubules.
Centrosome
Cilia
Flagella
Spindle apparatus
Microtubules provide structure and maintain cytoplasmic organization

10. Microtubule Examples: Cilia and Flagella
In animal cells, microtubules radiate outward to the cell periphery from a centrosome. This arrangement helps maintain a cell’s shape and allows it to withstand compression.
Microtubules also provide tracks for the transport of material from one part of the cell to another.
They are found in cilia and flagella, which propel the movement of cells or the movement of substances surrounding cells.
They are also found in the spindle apparatus that separates replicated chromosomes during cell division.

11. Microfilaments Narrowest diameter
Made of double helix of actin proteins
Microfilaments
are polymers of actin monomers that are arranged into a helix.
are the thinnest of the three cytoskeletal fibers and are present in various locations in the cytoplasm.
are relatively short and extensively branched just beneath the plasma membrane of a cell.
reinforce the plasma membrane and organize the proteins associated with it.
Beneath PM
Microvilli
Microfilaments also provide structural support in the shape of the cell.

12. Microfilament Example
The epithelial cells of the small intestine contain bundles of microfilaments that are found in the microvilli found on the surface of the cell. Longer bundles of microfilaments form a band that extends around the circumference of epithelial cells. This band is attached to a cell junction that connects it to its neighbors.
This band provides a great deal of structural support to the individual epithelial cells as well as the entire layer of epithelial cells.
Microfilaments also take part in:
Transport of materials inside cells
The shortening of a muscle cell during contraction
The separation of the daughter cells at the end of animal cell division
Both microtubules and microfilaments are dynamic structures and can assemble
/disassemble rapidly.

13. Intermediate Filaments
Intermediate filaments have a diameter intermediate to that of the microfilaments and microtubules. They are polymers of intermediate filament proteins that combine to form strong, cable-like structures in the cells, providing mechanical strength.
The proteins making up intermediate filaments differ from one cell type to the other. There are over 100 different kinds of intermediate filaments.
Intermediates provide structure for many types of cells and are made of proteins that
vary for the cell type. They are not dynamic structures.

14. Intermediate Filament Examples
Proteins can be:
Keratins
Vimentins
Neurofilaments
Lamins
Depending on cell type
In epithelial cells, the intermediate filament subunits are keratins. In fibroblasts, they are vimentins. And in neurons, they are neurofilaments.
Lamins are intermediate filaments found inside the nucleus, where they support the nuclear envelope.

15. Intermediate Filament Examples
Cytoplasmic side of desmosomes;
Gives tremendous strength to
epithelium of skin
Many intermediate filaments become attached at the cytoplasmic side of cellular junctions called desmosomes. This anchoring provides strong support for the cells, greatly strengthening the epithelial tissue, which allows the skin to withstand the stress it endures daily.

16. Intermediate Filament Defects: Epidermolysis Bullosa
Defective keratin genes
Intermediate filaments
do not polymerize
Weakens epidermis
Fragile skin; blisters
Genetic defects that disrupt the intermediate filament network have severe consequences. Individuals with epidermolysis bullosa have defective keratin genes. As a result, intermediate filaments do not polymerize properly, weakening the connections between the layers of cells that make up the epidermis.
This causes the outer layers of the epidermis to detach, resulting in extremely fragile skin that blisters in response to the slightest trauma.

17. How do doctors test for the spread of cancer?
Lymph nodes are meant to catch stranded fluid in various parts of the body
If a person is diagnosed with skin cancer—melanoma-- doctors can remove the nearby lymph node and check it for intermediate filament keratins from melanocytes
Since these intermediate filaments are not normally in lymph nodes, this can help the doctor determine how advanced the cancer is/course of treatment
Each part of the body drains to a specific lymph node. If a patient is diagnosed with melanoma cancer, a surgeon can remove the lymph node that drains the area of the body where the cancer is and a pathologist will examine the cells of the lymph node for the presence of intermediate filaments from melanocytes (melanocyte keratins). Since the lymph node does not normally contain these intermediate filaments, it helps the doctors determine how advanced the cancer is and the course of treatment.

18. Microtubules and Microfilaments Are Always Changing
+ Ends
Faster growing
Project outward toward PM
Microtubules and microfilaments are always changing. They become longer by the addition of subunits to their ends and shrink by the loss of subunits.
Usually, these polymers grow faster at one end than the other. The faster-growing end is called the plus end and the slower-growing end is called the minus end.
In animal cells, the minus ends of microtubules are positioned at the organizing center of the centrosome and the plus ends project outward toward the plasma membrane.
Microtubules also undergo random cycles of rapid shrinkage (depolymerization) followed by slower growth (polymerization).
Ends
Slower growing
At MTOC of centrosomes

19. Dynamic Instability Polymerization Depolymerization
These cycles of polymerization (growth) and depolymerization (shrinkage) in microtubules are called dynamic instability.
The dramatic shrinkage is often called microtubule catastrophe and takes place because the plus end of a microtubule is structurally unstable. T
his process may seem undesirable, but it allows microtubules to explore the space of the cell by growing into new areas and then shrinking back.
Depolymerization
Microtubules go through rounds of growth and rapid shrinkage called dynamic instability

20. Types of Cellular Movement
10.3 The cytoskeleton interacts with motor proteins to allow movement of cells and substances within cells.
Cell movement itself
Change in cell shape
Movement of molecules/organelles within
In microtubules: dynein & kinesin bind to tubulin
In microfilaments: myosin binds to actin

21. Arrangement of Microtubules in Cilia
Dynein allows microtubules to slide past each other
Flagella whips; cilia rows
The microtubules in cilia and flagella are distributed in a “9+2” arrangement. Nine pairs of microtubules are located around the periphery of these organelles and two microtubules are at the center.
The outer microtubules are connected to the center pair by cross-linking proteins and to their neighbors by dynein molecules. Energy harvested by the hydrolysis of ATP powers the motion of cilia and flagella.
Dynein undergoes a conformational change that cause the pairs of microtubules to slide past each other. The sliding of the microtubules results in a whiplike motion in the case of flagella and an oarlike rowing in the case of cilia.
Flagella and cilia contain microtubules that propel cells through aqueous environments. 21

22. Vesicle Movement within the Cell using Microtubules
Kinesin moves cargo
toward + end
Dynein moves cargo
toward - end
Microtubules also function as tracks for transport within the cell.
The difference here is that the motor proteins kinesin and dynein are used.
Kinesin moves the cargo towards the plus end of the microtubule while dynein moves it toward the minus end.
The energy for this movement is driven by conformational changes in the motor proteins and is powered by ATP.
Microtubules also function as tracks…..i.e. for chromosome movement during mitosis 22

23. Kinesin and Dynein at Work
Fish, amphibian embryos have melanophores
Move pigments around cell in response to hormone or
neuronal signals
Allow these animals to change color
Melanin granules in melanophores move along
microtubules transported by kinesin and dyein
Specialized skin cells, melanophores, are present in some vertebrates. They are similar to melanocytes in that they contain pigment, but they differ because they move the pigment granules around the cell in response to hormones or neuronal signals. This allows animals such as fish and amphibian embryos to change color.
The melanin granules in the melanophores move back and forth along microtubules transported by kinesin and dynein. Kinesin moves the granules out toward the plus end of the microtubule during dispersal and dynein moves them back toward the minus end during aggregation. 23

24. Muscle Contraction
Microfilaments and microtubules have some capacity to move on their own (by polymerization and depolymerization), but this movement is limited. When joined with motor proteins, they are able to cause large movements.
The shortening of a muscle cell is driven by interactions between the motor protein myosin and actin microfilament.
Myosin binds to actin and undergoes a conformational change. As a result, the actin microfilaments slide relative to myosin causing the cell to contract, or shorten.
Muscle shortening is by the binding of motor protein myosin with actin microfilaments

25. Cell Crawling Single-celled amoebas WBC Actin polymerization
Single-celled amoebas and mammalian white blood cells rely on actin polymerization to get from one place to another.
Commonly, new microfilaments are assembled and extended at one end of the cell and existing microfilaments are pulled together at the other end. This polymerization exerts a considerable amount of force, enough to push the plasma membrane out into a thin, sheetlike structure called a lamellipodium.
Bundles of actin filaments at the other end of the cell contract by the interactions of myosin and actin squeezing the cytoplasm and its contents forward toward the lamellipodium. The edge of the cell where the lamellipodium forms is called the leading edge, and the end where contraction takes place is called the trailing edge. The repeated action of this process results in cellular movement.
These leading and trailing edges are subject to change at any time depending on the needs of the cell and what is triggered by the cell-surface receptors.
Microfilaments enable cells to move by crawling across a surface or through a tissue

26. Cell Adhesion
10.4 Cells adhere to each other and to the ECM by means of cell adhesion molecules
and junctional complexes.
ECM:
A meshwork of proteins
and polysaccharides
outside cells
Cell adhesion molecules
Proteins that stick cells to each other and to ECM
Multicellular organisms are made up of much more than cells. The cells in most tissues and organs are connected to a complex meshwork of proteins and polysaccharides known as the extracellular matrix.
Cells are attached to one another and to the extracellular matrix by cell-surface proteins called cell-adhesion molecules. The regions where cells adhere to other cells or the extracellular matrix are called cellular junctions.
In 1907, H.V. Wilson noted that, if he pressed a sponge through a fine cloth, he would break it up into individual cells. If he swirled the cells together, they would coalesce back into a group resembling a sponge. He also noted that, if he mixed up individual cells from two different sponges, the cells sorted themselves out and coalesced by species.
Cell junctions
Where cells stick to each
other or to ECM

27. Cell Adhesion
Johannes Holtfreter observed that, if he took neural cells and skin cells from an amphibian embryo and treated them the same way that Wilson had treated sponge cells, the embryonic cells would sort themselves according to tissue type.
It was determined that cells can sort themselves because of the presence of various cell-adhesion molecules in the cell membrane. A number of cell-adhesion molecules are known, but the cadherins are especially important in the adhesion of cells to other cells.

28. Cadherins Cadherins: Transmembrane proteins
Allow cells to stick to other cells
Increases the strength of tissues & organs
Link to cytoskeleton
Found in adherens junctions & desmosomes
Cadherins are transmembrane proteins. The extracellular domain of a cadherin molecule binds to the extracellular domain of a cadherin of the same type on an adjacent cell.
The cytoplasmic portion of the cadherin is linked to the internal cytoskeleton.
This arrangement provides structural continuity from the cytoskeleton of one cell to the cytoskeleton of another, increasing the strength of tissues and organs.

29. Integrins Integrins: Transmembrane proteins
Allow cells to stick to ECM
Reinforcement to tissues under physical
stress
Link to cytoskeleton
Cells also attach to the extracellular matrix. This attachment provides structural reinforcement to tissues under physical stress.
The cell-adhesion molecules that enable cells to adhere to the extracellular matrix are called integrins.
These too are transmembrane proteins with their cytoplasmic domain linked to the cytoskeleton.
Integrins are present on the surface of virtually every animal cell.

30. Junctional Complexes Junctional complexes: Anchor cells to each other
Reinforced by cytoskeleton
Junctional complexes anchor cells to one another and are reinforced by the cytoskeleton.

31. Adherens Junctions and Desmosomes
Anchor cells to each other
Belt-like complex of cadherins
Reinforced by actin microfilaments
Desmosomes:
Button-like complex of cadherins
Reinforced by intermediate filaments
Cadherins are not distributed randomly in the plasma membrane but are located in adherens junctions and desmosomes. These complexes anchor cells to one another and are reinforced by the cytoskeleton.
An adherens junction is a beltlike junctional complex of cadherins that goes around the circumference of the cell.
In the cytoplasm, the belt of cadherins attach to a band of actin microfilaments.
In the extracellular space, the cadherins attach to other cadherins in the adherens junctions of adjacent cells.
Desmosomes are buttonlike points of adhesion that hold the plasma membrane of adjacent cells together.
Cadherins are at work, too, strengthening the connection between cells in a manner similar to adherens junctions.
The cadherins in the desmosome of one cell bind to the cadherins in the desmosomes of adjacent cells.
The cytoplasmic domains of these cadherins are linked to intermediate filaments of the cytoskeleton.

32. Hemidesmosomes Hemidesmosome: Anchors epithelial cells to basal lamina
Integrins are the cell adhesion molecules
Epithelial cells are firmly anchored to the basal lamina by a version of the desmosome called a hemidesmosome. Integrins are the prominent cell adhesion molecules in hemidesmosomes. Their extracellular domains bind to the extracellular matrix proteins in the basal lamina and their cytoplasmic domains are linked to intermediate filaments of the cytoskeleton. 32

33. Interactions in Junctions, Adhesion Molecules, and Cytoskeletal Elements
Belt
Button/screw
Cellular junctions and cytoskeletal elements interact to create stable communities of cells in the form of tissues and organs. These interactions are specific with certain junctions associated with specific components of the cytoskeletal network. 33

34. Tight Junctions
Tight junction: belt that prevents passage of substances through spaces between cells
Not meant to anchor cells together
Adherens junctions and desmosomes provide strong connections between cells, but they do not prevent the free passage of materials through the spaces between the cells they connect.
Junctional complexes called tight junctions establish a seal between cells so that the only way a substance can travel from one side of a sheet of epithelial cells to the other is by means of one of the cellular transport mechanisms.
The function of tight junctions is not to anchor the cells together, but instead to prevent passage of materials in between cells.

35. Gap Junctions and Plasmodesmata
Connections between cells to allow materials through
Some junctions such as gap junctions of animal cells and plamodesmata of plant cells are connections between the plama membranes of adjacent cells that permit materials to pass directly from the cytoplasm of one cell to the cytoplasm of another.
Gap junctions are formed when a set of integral membrane proteins arranged in a ring connects to a similar ring of proteins in the membrane of another cell. Ions and signaling molecules pass through these junctions, allowing cells to communicate.
Plasmodesmata allow plant cells to transfer RNA molecules and proteins because they are much larger than gap junctions. In plasmodesmata, the plasma membranes between the two cells are continuous. They allow plants to send signals to one another despite being enclosed within rigid cell walls.
Gap junctions are in animal cells
Plasmodesmata are in plant cells
Both are communicating channels

36. Extracellular Matrix (Plants)
10.5 The extracellular matrix (ECM) provides structural support and information cues.
ECM is an insoluble mesh of proteins and polysaccharides secreted by the cell
In plants it is the external cell wall
Provides structural support to plants
Composed of 3 layers
In plants, the extracellular matrix is the cell wall. It provides the support needed by individual cells and, by forming an interconnected network between cells, provides the support for the entire organism.
The plant cell wall is composed of three layers.

37. Layers of the Cell Wall Cell wall:
Middle lamella:
Made of carbohydrates
Main mechanism by which plant cells adhere to one another
2. Primary cell wall
Made of cellulose fibers, pectin, and several other proteins
Thin and flexible
3. Secondary cell wall
Made of cellulose and lignin
Rigid
Lignin is the substance that hardens the cell wall and makes it water resistant.
When a plant cell grows, additional cell-wall components must be synthesized to expand the area of the wall. Unlike the components secreted by animal cells, the cellulose polymer is assembled outside the cell, on the extracellular surface of the plasma membrane.
Cell wall:
Middle lamina (outermost)….sticky carbohydrate
Primary cell wall (thin/flexible)…..cellulose, pectins
Secondary cell wall (closest to PM, rigid)…cellulose, lignin

38. Extracellular Matrix (Animals)
In animals, cells of connective tissue
are in background matrix of ECM fibers
Connects & supports
Collagen: main strength protein
Elastin: stretchy
Laminin
The extracellular matrix of animal cells is secreted by cells in a mixture of proteins and polysaccharides. It is composed of large fibrous proteins including collagen, elastin, and laminin.
These proteins are found in the gel-like polysaccharide matrix.

39. Collagen Primary structural support protein in animals
Collagen is the most abundant protein in the extracellular matrix of animals and the most abundant animal protein on the planet. There are more than 20 different forms of collagen, and it makes up over a quarter of the protein present in the body.
Ninety percent of collagen is type I collagen, which is present in the dermis of your skin, where it provides support.
It is composed of intertwined fibers that make it stronger than if it were a single fiber of the same diameter. It consists of three polypeptides wound around one another in a triple helix. A bundle of these molecules forms a fibril and fibrils are assembled into fibers.

40. Basal Lamina
Special layer of ECM beneath epithelial tissue; also called basement membrane;
it anchors cells using integrins in hemidesmosomes
The basal lamina is a specialized layer of the extracellular matrix that is present beneath all epithelial tissues.
Its role is to provide a structural foundation for epithelial tissues. It is made of several proteins including a type of collagen that provides flexible support to the epithelial sheet and also provides a scaffold on which other proteins are assembled.

41. The Extracellular Matrix Influence on Cell Shape
ECM, in addition to structural support, also influences cell shape, movement, and
gene expression
Cell shape is influenced by the structure of the extracellular matrix as well as by the composition of it.
Fibroblasts grown on a two-dimensional matrix attach and are flattened. But when grown in a three-dimensional matrix, they are spindle-shaped and look as they do in vivo.

42. The Extracellular Matrix Influence on Cell Shape
The composition of the extracellular matrix also influences the shape of the cell.
Here, neurons maintained in the absence of the extracellular matrix protein laminin attach but do not take the shape of a typical nerve cell.
However, when laminin is added to the culture, the neurons develop extensions resembling axons and dendrites of normal nerve cells.
Without laminin
With laminin

43. The Extracellular Matrix Influence on Gene Expression
Joan Caron hypothesized that a specific protein in the extracellular matrix was responsible for the expression of albumin from liver cells.

44. Caron’s Experiments
Caron showed that a specific ECM protein, laminin, influences the expression of
albumin by hepatocytes.
To test her hypothesis, Caron cultured hepatocytes on a thin layer of type I collagen, which did not induce albumin synthesis. (Figure 1)
Next, she added a mixture of several different extracellular matrix proteins to the culture and looked for changes in albumin gene expression and protein secretion into the media. (Figure 2)

45. Caron’s Experiments
She then tested individual extracellular matrix proteins from the mixture to see which one was responsible for the increase in albumin gene expression. Caron found that when she cultured cells on collagen with a combination of three extracellular matrix proteins—laminin, type IV collagen, and heparin sulfate proteoglycan (HSPG)—the cells synthesized albumin mRNA and secreted albumin protein for several weeks, but if she cultured the cells on collagen alone, they did not (Figures 1 & 2, slide 43).
In addition, when she tested individual extracellular matrix proteins, she found that laminin, but not any of the other proteins, caused an increase in albumin gene expression. Caron was able to support her hypothesis by these experiments, a specific extracellular matrix protein, laminin, influences the expression of albumin by hepatocytes.

46. The Extracellular Matrix and Cancer
Integrins help metastatic tumor cells cross basal lamina and spread to distant sites.
Drugs targeting this integrin protein are currently in clinical trials.
For a malignant cancer cell to metastasize, it must break free from the main tumor and colonize a different site in the body. Metastatic tumor cells have an enhanced ability to adhere to extracellular matrix proteins, especially those in the basal lamina.
In order to metastasize, the cell must enter and leave the blood stream through capillaries. Since all blood vessels have a basal lamina, a metastatic tumor cell needs to cross the basal lamina at least twice.
Since cells attach to basal lamina proteins by means of integrins, many studies have compared the integrins in metastatic and non-metastatic cells in the search for potential treatment.
In laboratory tests, blocking these integrins eliminates the melanoma cell’s ability to cross an artificial basal lamina. Drugs targeting this integrin protein are currently in clinical trials. 46