unit 2 week 3 pt 1 Flashcards
How do materials outside the plasma membrane affect the life of a cell?
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.
What types of cells interact with extracellular materials?
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.
What role do extracellular materials play in tissues?
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.
What is the difference between the epidermis and dermis in skin?
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.
How do fibroblasts in the dermis interact with their environment?
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.
What is the glycocalyx and what is its role?
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.
What is the extracellular matrix (ECM)?
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.
How does the ECM affect cell behavior?
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.
What is the basement membrane and what functions does it serve?
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.
How does the basement membrane impact kidney function?
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.
What is the structure of ECM in cells not on a basement membrane?
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.
What are the major components of the ECM?
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.
How do the proteins in the ECM function?
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.
What are collagens, and why are they important?
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.
What types of cells produce collagen?
Collagen is primarily produced by fibroblasts in connective tissues, but also by smooth muscle cells and epithelial cells.
How many types of collagen are there, and how do they differ?
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
What are the structural features of collagen molecules?
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.
What happens if collagen chains are not hydroxylated?
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.
What are fibrillar collagens and how do they function?
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.
How do collagen fibrils contribute to the function of tendons and corneas?
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.
What happens if collagen formation is abnormal?
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).
What is type IV collagen, and where is it found?
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.
What is the effect of mutations in type IV collagen genes?
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.
What are proteoglycans, and where are they found?
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.
What is the structure of glycosaminoglycans (GAGs)?
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.
How do proteoglycans form large complexes?
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.
What are the properties of proteoglycans, and how do they contribute to the extracellular matrix (ECM)?
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.
How do proteoglycans function in bone?
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.
What role do proteoglycans play in cell-cell signaling?
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.
What are the health-related uses of GAGs?
Both sulfated and nonsulfated GAGs are commonly taken as health supplements, often to improve skin and joint health.
What is fibronectin, and what is its role in the extracellular matrix (ECM)?
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.
What is the structure of fibronectin?
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.
How do fibronectin molecules interact with other ECM components?
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.
How does fibronectin bind to cell receptors?
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.
What is the role of fibronectin during embryonic development?
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.
How does fibronectin contribute to organ formation?
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.
What experimental evidence shows the importance of fibronectin in development?
Inactivating fibronectin in salivary glands using antibodies prevents cleft formation and branching, demonstrating its critical role in these developmental processes.
What is laminin, and what is its structure?
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.
What role does laminin play in cell migration and development?
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.
How does laminin interact with other molecules?
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.
What is the importance of laminin in basement membrane formation?
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.
How is the extracellular matrix (ECM) dynamic?
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.
What is the role of matrix metalloproteinases (MMPs) in ECM degradation?
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.
What can happen if MMP activity is excessive or inappropriate?
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.
What are integrins?
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.
What is the structure of integrins?
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.
How many different types of integrins exist?
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.
What is the significance of the bent and upright conformation of integrins?
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.
What is the significance of the bent and upright conformation of integrins?
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.
What is inside-out signaling in integrins?
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.
What is outside-in signaling in integrins?
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.
How do integrins affect cell survival and growth?
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.
What is the clinical significance of integrins?
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.
What role does the RGD sequence play in integrin function?
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.
Can integrins bind to multiple ligands?
Yes, individual integrins can bind to various extracellular components, and cells often express multiple types of integrins, allowing them to interact with different ligands.
What is the role of integrins in connecting the extracellular matrix (ECM) to the cytoskeleton?
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.
What are focal adhesions and how are they formed?
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.
How do focal adhesions contribute to cell locomotion?
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.
What is mechanotransduction, and how is it related to focal adhesions?
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.
How do focal adhesions respond to mechanical forces applied by the cell?
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.
What effect does the strength of integrin-ligand bonds have on focal adhesion formation?
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.
How do mechanical forces affect gene expression in cells?
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.
How does substrate stiffness influence mesenchymal stem cell (MSC) differentiation?
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.
What are hemidesmosomes, and where are they found in the body?
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.
How are hemidesmosomes different from focal adhesions?
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.
What role do integrins play in hemidesmosomes?
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.
What is the significance of hemidesmosomes in health and disease?
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.
What genetic diseases are associated with hemidesmosomal dysfunction?
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.
