unit 2 week 3 pt 1

Question 1

How do materials outside the plasma membrane affect the life of a cell?

Answer 1

Materials outside the plasma membrane play an important role in the life of a cell, influencing processes such as cell migration, growth, differentiation, and the three-dimensional organization of tissues and organs during embryonic development.

Question 2

What types of cells interact with extracellular materials?

Answer 2

Most cells in multicellular organisms interact with extracellular materials. Even cells with no fixed relationship within a tissue, like white blood cells, interact with other cells and extracellular materials in specific ways.

Question 3

What role do extracellular materials play in tissues?

Answer 3

Extracellular materials help maintain the organization of tissues and cells, contributing to the three-dimensional structure and functionality of tissues and organs, especially during embryonic development.

Question 4

What is the difference between the epidermis and dermis in skin?

Answer 4

The epidermis is a type of epithelial tissue, consisting largely of closely packed cells attached to one another and an underlying noncellular layer. The dermis, in contrast, is connective tissue and consists mostly of extracellular material, including fibers.

Question 5

How do fibroblasts in the dermis interact with their environment?

Answer 5

Fibroblasts in the dermis have receptors on their plasma membrane that mediate interactions between the cell and its environment. These receptors are connected to cytoplasmic proteins, allowing the transmission of messages between the cell and its surroundings.

Question 6

What is the glycocalyx and what is its role?

Answer 6

The glycocalyx is a layer of carbohydrate projections on the outer surface of the plasma membrane, formed by integral membrane proteins and lipids with sugar chains. It mediates cell-cell and cell-substratum interactions, provides mechanical protection, serves as a barrier to particles, and binds regulatory factors that act on the cell surface.

Question 7

What is the extracellular matrix (ECM)?

Answer 7

The ECM is an organized network of secreted molecules that surrounds and supports cells and tissues. It provides physical, biochemical, and mechanical signals that regulate the shape and activities of cells, and plays key roles in maintaining cell functions like synthesis and secretion.

Question 8

How does the ECM affect cell behavior?

Answer 8

The ECM regulates cell shape and activities by providing biochemical and mechanical signals. For example, when ECM is digested, cells like cartilage or mammary gland epithelial cells show reduced synthetic and secretory activity. Adding ECM back restores their function.

Question 9

What is the basement membrane and what functions does it serve?

Answer 9

The basement membrane (or basal lamina) is a continuous sheet that surrounds cells like nerve fibers, muscles, and fat cells, and underlies epithelial tissues and blood vessels. It provides mechanical support, maintains cell survival, supports cell migration, separates tissues, and serves as a barrier to macromolecule passage.

Question 10

How does the basement membrane impact kidney function?

Answer 10

In the kidney, the basement membrane acts as a barrier that prevents proteins from leaking out of blood vessels and into tissues. Abnormal thickening of the basement membrane, especially in diabetics, can lead to kidney failure by impairing filtration.

Question 11

What is the structure of ECM in cells not on a basement membrane?

Answer 11

Cells not on a basement membrane, such as fibroblasts in connective tissue, are surrounded by a less organized ECM consisting largely of fibrils. This ECM provides structure and support but is not as structured as the basement membrane.

Question 12

What are the major components of the ECM?

Answer 12

The major components of the ECM include collagens, proteoglycans, fibronectin, and laminin. These proteins have binding sites that allow them to interact with each other and with cell surface receptors, forming a connected network.

Question 13

How do the proteins in the ECM function?

Answer 13

Proteins in the ECM act as scaffolds, trail markers, and structural elements like girders, wires, and glue, providing mechanical support and facilitating cellular interactions. Changes in the amino acid sequences of these proteins can lead to disorders.

Question 14

What are collagens, and why are they important?

Answer 14

Collagens are fibrous glycoproteins found only in extracellular matrices. They are the most abundant protein in the human body, constituting more than 25% of total protein. Collagens provide high tensile strength, meaning they resist pulling forces, and are crucial for the structure and function of connective tissues.

Question 15

What types of cells produce collagen?

Answer 15

Collagen is primarily produced by fibroblasts in connective tissues, but also by smooth muscle cells and epithelial cells.

Question 16

How many types of collagen are there, and how do they differ?

Answer 16

There are 28 distinct types of collagen in humans. Each type is found in specific locations in the body, and different types may coexist in the same extracellular matrix (ECM), providing functional complexity and varied structural and mechanical properties when mixed.
-1-5 is most abundant
-Type I:
The most abundant type, found in skin, bones, tendons, ligaments, and organs, providing structure and tensile strength.
Type II:
Primarily found in cartilage, supporting joint function and providing flexibility.
Type III:
Found in muscles, arteries, and organs, often working alongside type I collagen, providing elasticity and support.
Type IV:
Found in the layers of skin and forms the basal lamina, a layer of the basement membrane.
Type V:
Found in the cornea of the eyes, some layers of skin, hair and tissue of the placenta

Question 17

What are the structural features of collagen molecules?

Answer 17

Collagen molecules are trimers made up of three polypeptide chains called ? chains. These chains are wound into a rod-like triple helix. Collagen chains contain large amounts of proline, and many proline and lysine residues are hydroxylated, which is important for the stability of the triple helix.

Question 18

What happens if collagen chains are not hydroxylated?

Answer 18

If collagen chains are not hydroxylated, it can result in structural and functional problems in connective tissues, leading to diseases like scurvy, which is caused by a deficiency of vitamin C. Scurvy results in symptoms such as inflamed gums, tooth loss, poor wound healing, brittle bones, and weakened blood vessel linings.

Question 19

What are fibrillar collagens and how do they function?

Answer 19

Fibrillar collagens (types I, II, and III) assemble into rigid, cable-like fibrils that form thicker fibers. These fibrils provide structural support to tissues and are strengthened by covalent cross-links between lysine and hydroxylysine residues. They contribute to the mechanical strength of tissues like tendons and skin.

Question 20

How do collagen fibrils contribute to the function of tendons and corneas?

Answer 20

In tendons, collagen fibrils are aligned parallel to the tendon’s long axis, allowing them to resist pulling forces during muscular contraction. In the cornea, collagen fibrils are organized in distinct layers, providing both strength and transparency to the tissue, similar to the structure of plywood.

Question 21

What happens if collagen formation is abnormal?

Answer 21

Abnormal collagen formation can lead to various disorders. Excessive collagen production leads to fibrosis, where scar tissue replaces normal tissue in organs like the lungs (pulmonary fibrosis) or liver (cirrhosis). Mutations in collagen genes can cause conditions like osteogenesis imperfecta (fragile bones), dwarfism (due to altered cartilage properties), and Ehler-Danlos syndromes (hyperflexible joints and stretchy skin).

Question 22

What is type IV collagen, and where is it found?

Answer 22

Type IV collagen is nonfibrillar and is found in basement membranes. It forms a network that provides mechanical support and serves as a lattice for other extracellular materials. Unlike fibrillar collagens, type IV collagen has nonhelical segments and globular ends, which make it flexible and facilitate its lattice-like structure.

Question 23

What is the effect of mutations in type IV collagen genes?

Answer 23

Mutations in type IV collagen genes can lead to Alport syndrome, an inherited kidney disease where the glomerular basement membrane is disrupted, affecting kidney function.

Question 24

What are proteoglycans, and where are they found?

Answer 24

Proteoglycans are protein-polysaccharide complexes found in basement membranes and extracellular matrices. They consist of a core protein to which chains of glycosaminoglycans (GAGs) are covalently attached.

Question 25

What is the structure of glycosaminoglycans (GAGs)?

Answer 25

Glycosaminoglycans (GAGs) are composed of repeating disaccharides with the structure -A-B-A-B-, where A and B represent different sugars. They are highly acidic due to the presence of sulfate and carboxyl groups on the sugar rings.

Question 26

How do proteoglycans form large complexes?

Answer 26

Proteoglycans can form gigantic complexes by linking their core proteins to a molecule of hyaluronic acid, a nonsulfated GAG. These complexes can occupy a volume similar to that of a bacterial cell.

Question 27

What are the properties of proteoglycans, and how do they contribute to the extracellular matrix (ECM)?

Answer 27

Due to the negative charges on the sulfated GAGs, proteoglycans bind cations, which in turn attract water molecules. This creates a porous, hydrated gel that fills extracellular space, providing resistance to compression. Together with collagen, proteoglycans help give tissues like cartilage strength and resistance to deformation.

Question 28

How do proteoglycans function in bone?

Answer 28

In bone, proteoglycans, along with collagen, contribute to the structure of the extracellular matrix. However, bone matrix is further hardened by the impregnation of calcium phosphate salts.

Question 29

What role do proteoglycans play in cell-cell signaling?

Answer 29

Proteoglycans are involved in cell-cell signaling by binding to growth factors like fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). They help form stable signaling gradients by acting as a 'sink' for these molecules.

Question 30

What are the health-related uses of GAGs?

Answer 30

Both sulfated and nonsulfated GAGs are commonly taken as health supplements, often to improve skin and joint health.

Question 31

What is fibronectin, and what is its role in the extracellular matrix (ECM)?

Answer 31

Fibronectin is a protein in the extracellular matrix that interacts with other ECM components like collagen and proteoglycans. It helps form a network of interconnected proteins that provides structural support and stability to tissues.

Question 32

What is the structure of fibronectin?

Answer 32

Fibronectin consists of a linear array of approximately 30 Fn domains, which are modular building blocks. These domains combine to form larger functional units, enabling the protein to interact with various components in the ECM and cell receptors.

Question 33

How do fibronectin molecules interact with other ECM components?

Answer 33

Fibronectin molecules contain binding sites for ECM components like collagen, proteoglycans, and other fibronectin molecules. These interactions help create a stable, interconnected ECM network. Mechanical forces can also enhance these interactions by unfolding fibronectin's domains, exposing hidden binding sites.

Question 34

How does fibronectin bind to cell receptors?

Answer 34

Fibronectin contains binding sites for receptors on the cell surface, facilitating stable attachment between the ECM and the cell. This interaction plays a crucial role in cell attachment and shape, as seen in cultured endothelial cells.

Question 35

What is the role of fibronectin during embryonic development?

Answer 35

During embryonic development, fibronectin guides migrating cells along specific pathways, such as those followed by neural crest cells. These pathways are rich in fibronectin fibrils, which help direct the migration of cells to different parts of the embryo.

Question 36

How does fibronectin contribute to organ formation?

Answer 36

Fibronectin is essential in the branching process of organ formation, such as in the salivary gland, kidney, and lung. It helps create clefts in the epithelial layer, and disrupting fibronectin activity prevents cleft formation, as shown in the salivary gland example.

Question 37

What experimental evidence shows the importance of fibronectin in development?

Answer 37

Inactivating fibronectin in salivary glands using antibodies prevents cleft formation and branching, demonstrating its critical role in these developmental processes.

Question 38

What is laminin, and what is its structure?

Answer 38

Laminin is a family of extracellular glycoproteins made up of three polypeptide chains linked by disulfide bonds, forming a cross-like structure with three short arms and one long arm. At least 15 different laminins have been identified.

Question 39

What role does laminin play in cell migration and development?

Answer 39

Laminins influence cell migration, growth, and differentiation. For instance, they are crucial in the migration of primordial germ cells from the yolk sac to the developing gonad, where they form sperm or eggs. These cells adhere to laminin molecules during migration.

Question 40

How does laminin interact with other molecules?

Answer 40

Laminins bind tightly to cell-surface receptors and can also interact with other laminin molecules, proteoglycans, and components of basement membranes, forming interconnected networks with type IV collagen molecules.

Question 41

What is the importance of laminin in basement membrane formation?

Answer 41

Laminin and type IV collagen form separate but interconnected networks in basement membranes, giving them both strength and flexibility. Without laminin, basement membranes do not form, leading to embryo death in mice around the time of implantation.

Question 42

How is the extracellular matrix (ECM) dynamic?

Answer 42

The ECM is not static; it has dynamic properties. ECM fibrils can stretch and contract in response to cell forces, and the matrix undergoes continual degradation and reconstruction. This allows for remodeling during development and tissue repair.

Question 43

What is the role of matrix metalloproteinases (MMPs) in ECM degradation?

Answer 43

MMPs are zinc-containing enzymes that degrade ECM components, facilitating tissue remodeling, embryonic cell migration, wound healing, and blood vessel formation. MMPs are also involved in the degradation of extracellular materials during normal development and repair.

Question 44

What can happen if MMP activity is excessive or inappropriate?

Answer 44

Excessive or inappropriate MMP activity can lead to various diseases, including arthritis, tooth and gum disease, blood clots, heart attacks, and tumor progression. Mutations in MMP genes can also cause inherited skeletal disorders.

Question 45

What are integrins?

Answer 45

Integrins are membrane proteins found only in animals that play a key role in connecting the extracellular and intracellular environments. They bind to extracellular molecules (ligands) and interact with intracellular proteins to influence cell processes.

Question 46

What is the structure of integrins?

Answer 46

Integrins are composed of two noncovalently linked polypeptide chains: an ? chain and a ? chain. The ? and ? subunits form a globular extracellular head connected to the membrane by elongated 'legs.' The subunits have a small cytoplasmic domain with about 20 to 70 amino acids.

Question 47

How many different types of integrins exist?

Answer 47

There are 18 different ? subunits and 8 different ? subunits, resulting in about two dozen different integrins on the surface of cells. Some subunits, like ?1, appear in multiple integrins, while others, like ?v, are found in 5 integrins.

Question 48

What is the significance of the bent and upright conformation of integrins?

Answer 48

The bent conformation represents the inactive state of the integrin, where it cannot bind to a ligand. When the integrin is activated, such as through binding of talin, it assumes an upright conformation, which allows it to bind to ligands.

Question 49

What is the significance of the bent and upright conformation of integrins?

Answer 49

The bent conformation represents the inactive state of the integrin, where it cannot bind to a ligand. When the integrin is activated, such as through binding of talin, it assumes an upright conformation, which allows the protein to interact with its ligands.

Question 50

What is inside-out signaling in integrins?

Answer 50

Inside-out signaling refers to the process by which changes inside the cell (e.g., binding of talin to integrins) cause conformational changes in integrins, enhancing their ability to bind ligands and strengthening interactions between the cell and its extracellular matrix.

Question 51

What is outside-in signaling in integrins?

Answer 51

Outside-in signaling occurs when integrins bind to extracellular ligands (like fibronectin or collagen). This binding induces a conformational change at the cytoplasmic end of the integrin, leading to activation of proteins that influence cell behavior, such as actin polymerization and kinase activation.

Question 52

How do integrins affect cell survival and growth?

Answer 52

Integrins are crucial for cell survival. Normal cells require integrin binding to a substrate to survive and divide. Malignant cells, however, can grow without such binding, which contributes to their ability to survive in suspension cultures, unlike normal cells.

Question 53

What is the clinical significance of integrins?

Answer 53

Integrins are involved in platelet aggregation, which is important for blood clotting. Drugs targeting integrins, like Aggrastat and Integrelin, are used to prevent blood clots, and integrin-targeting antibodies are used in treatments for conditions such as multiple sclerosis.

Question 54

What role does the RGD sequence play in integrin function?

Answer 54

The RGD (arginine-glycine-aspartic acid) sequence is found in extracellular proteins like fibronectin and laminin. This sequence is critical for binding to integrins, facilitating cell adhesion to the extracellular matrix and initiating signaling pathways.

Question 55

Can integrins bind to multiple ligands?

Answer 55

Yes, individual integrins can bind to various extracellular components, and cells often express multiple types of integrins, allowing them to interact with different ligands.

Question 56

What is the role of integrins in connecting the extracellular matrix (ECM) to the cytoskeleton?

Answer 56

The cytoplasmic domains of integrins contain binding sites for cytoplasmic proteins that link integrins to actin filaments in the cytoskeleton. This connection between the ECM and cytoskeleton is evident in specialized structures called focal adhesions and hemidesmosomes.

Question 57

What are focal adhesions and how are they formed?

Answer 57

Focal adhesions are discrete, dynamic sites where cells attach to a substratum, formed by integrins on the plasma membrane interacting with actin filaments through adaptor proteins like talin, α-actinin, and vinculin.

Question 58

How do focal adhesions contribute to cell locomotion?

Answer 58

Focal adhesions play a key role in cell locomotion by developing transient interactions with extracellular materials. They can create or respond to mechanical forces, as they contain actin and myosin, which are major contractile proteins in cells.

Question 59

What is mechanotransduction, and how is it related to focal adhesions?

Answer 59

Mechanotransduction is the process by which mechanical forces applied to the cell surface are converted into biochemical signals inside the cell. Focal adhesions act as mechanosensors by recognizing the physical properties of the environment, triggering cellular responses through signal conversion.

Question 60

How do focal adhesions respond to mechanical forces applied by the cell?

Answer 60

When mechanical forces, like pulling forces, are exerted on the focal adhesions, they can induce conformational changes in adaptor proteins such as talin. These changes expose binding sites, which recruit additional proteins, activating protein kinases like Src and FAK that transmit signals throughout the cell.

Question 61

What effect does the strength of integrin-ligand bonds have on focal adhesion formation?

Answer 61

The strength of integrin-ligand bonds, measured in piconewtons (pN), influences the formation of focal adhesions. Stronger bonds (e.g., 56 pN) allow the formation of stable focal adhesions and actin stress fibers, while weaker bonds (e.g., 43 pN) do not.

Question 62

How do mechanical forces affect gene expression in cells?

Answer 62

Mechanical forces applied to focal adhesions can activate protein kinases like FAK or Src, which phosphorylate substrates and transmit signals to the cell nucleus. This activation can lead to changes in gene expression, influencing cellular behavior.

Question 63

How does substrate stiffness influence mesenchymal stem cell (MSC) differentiation?

Answer 63

The stiffness of the substrate on which MSCs are grown affects their differentiation. On soft substrates, MSCs differentiate into nerve cells. On stiffer substrates, they differentiate into muscle cells, and on even stiffer substrates, they differentiate into osteoblasts, which give rise to bone cells.

Question 64

What are hemidesmosomes, and where are they found in the body?

Answer 64

Hemidesmosomes are specialized adhesive structures found at the basal surface of epithelial cells, where they anchor the cells to the underlying basement membrane. They are the tightest form of attachment between a cell and its extracellular matrix in the body.

Question 65

How are hemidesmosomes different from focal adhesions?

Answer 65

Hemidesmosomes have a dense plaque on the inner surface of the plasma membrane, with filaments extending into the cytoplasm. Unlike the actin filaments of focal adhesions, hemidesmosomes contain thicker keratin filaments, which are classified as intermediate filaments and serve a supportive function.

Question 66

What role do integrins play in hemidesmosomes?

Answer 66

In hemidesmosomes, membrane-spanning integrins, such as α6β4, link the keratin filaments to the extracellular matrix. These integrins also transmit signals from the ECM that influence the shape and activities of the attached epithelial cells.

Question 67

What is the significance of hemidesmosomes in health and disease?

Answer 67

Hemidesmosomes are crucial for stable cell adhesion to the ECM. Disorders like bullous pemphigoid, an autoimmune disease where antibodies attack hemidesmosomal proteins, can cause the epidermis to lose attachment to the basement membrane, leading to severe skin blistering.

Question 68

What genetic diseases are associated with hemidesmosomal dysfunction?

Answer 68

Inherited blistering diseases like epidermolysis bullosa can result from genetic alterations in hemidesmosomal proteins, such as the α6 or β4 integrin subunits, collagen VII, or laminin-5, leading to skin blistering due to weakened attachment between the epidermis and basement membrane.