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Questions and Answers
The ______ provides structural integrity to connective tissues.
The ______ provides structural integrity to connective tissues.
extracellular matrix
The ______ serves as a scaffold for cell organisation in tissues.
The ______ serves as a scaffold for cell organisation in tissues.
basal lamina
MMPs are used by dendritic cells to degrade ______.
MMPs are used by dendritic cells to degrade ______.
extracellular matrix
The ECM can immobilize ______ gradients, influencing cell migration.
The ECM can immobilize ______ gradients, influencing cell migration.
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Components of the ECM include ______, fibrous proteins, and adhesive glycoproteins.
Components of the ECM include ______, fibrous proteins, and adhesive glycoproteins.
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The ECM regulates cell ______, polarity, differentiation, and function.
The ECM regulates cell ______, polarity, differentiation, and function.
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The ECM provides resistance to compressive forces and elasticity, important for ______ tissues.
The ECM provides resistance to compressive forces and elasticity, important for ______ tissues.
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Different forms and arrangements of ECM components result in varying ______ properties among tissues.
Different forms and arrangements of ECM components result in varying ______ properties among tissues.
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The basal lamina connects the epidermis to the ______.
The basal lamina connects the epidermis to the ______.
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Basal lamina acts as a ______ for tissue regeneration.
Basal lamina acts as a ______ for tissue regeneration.
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One of the functions of the basal lamina is to determine cell ______.
One of the functions of the basal lamina is to determine cell ______.
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Fibroblasts and chondroblasts are types of cells that ______ extracellular matrix components.
Fibroblasts and chondroblasts are types of cells that ______ extracellular matrix components.
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Matrix metalloproteases (MMPs) are involved in the ______ of the extracellular matrix.
Matrix metalloproteases (MMPs) are involved in the ______ of the extracellular matrix.
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Cell surface localization of proteases, such as MMP-14, is essential for their ______.
Cell surface localization of proteases, such as MMP-14, is essential for their ______.
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The extracellular matrix can be oriented by cells such as ______.
The extracellular matrix can be oriented by cells such as ______.
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Cellular proteases are implicated in processes like inflammation and ______ invasion.
Cellular proteases are implicated in processes like inflammation and ______ invasion.
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Laminin is a heterotrimer made up of , , and ______ chains.
Laminin is a heterotrimer made up of , , and ______ chains.
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The extracellular matrix is organized by cells that secrete ______ fibrils.
The extracellular matrix is organized by cells that secrete ______ fibrils.
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The outermost layer of skin is called the ______.
The outermost layer of skin is called the ______.
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In connective tissues, the ______ determines the tissue’s physical properties.
In connective tissues, the ______ determines the tissue’s physical properties.
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Tendons are characterized by their ropelike structure and high ______ strength.
Tendons are characterized by their ropelike structure and high ______ strength.
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Blood vessel walls are described as resilient and ______.
Blood vessel walls are described as resilient and ______.
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Cartilage provides both tensile strength and ______ properties.
Cartilage provides both tensile strength and ______ properties.
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Bone tissue is known for being rigid and ______.
Bone tissue is known for being rigid and ______.
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Elements such as ______ polysaccharide chains are important components of the extracellular matrix.
Elements such as ______ polysaccharide chains are important components of the extracellular matrix.
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Fibrous proteins like collagen and ______ provide structural integrity to tissues.
Fibrous proteins like collagen and ______ provide structural integrity to tissues.
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Adhesive ______ act as adapters in the extracellular matrix.
Adhesive ______ act as adapters in the extracellular matrix.
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The vitreous body of the eye consists of a transparent, jelly-like ______.
The vitreous body of the eye consists of a transparent, jelly-like ______.
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Type IX binds type II fibrils in ______
Type IX binds type II fibrils in ______
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Elastic fibres primarily consist of ______
Elastic fibres primarily consist of ______
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Fibronectin helps attach cells to the ______
Fibronectin helps attach cells to the ______
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The basal lamina is a thin, tough, flexible sheet of ______
The basal lamina is a thin, tough, flexible sheet of ______
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Elastic fibres are also covered in ______ made from glycoproteins.
Elastic fibres are also covered in ______ made from glycoproteins.
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The ______ provides structural support and a medium for cell signaling.
The ______ provides structural support and a medium for cell signaling.
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The ______ is a thin layer of ECM that supports epithelial cells.
The ______ is a thin layer of ECM that supports epithelial cells.
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Remodeling and degradation of the ECM are essential for ______ during development.
Remodeling and degradation of the ECM are essential for ______ during development.
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The ECM consists of proteins and polysaccharides, including ______, which provides tensile strength.
The ECM consists of proteins and polysaccharides, including ______, which provides tensile strength.
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Cellular components in the ECM like ______ play a crucial role in cell communication.
Cellular components in the ECM like ______ play a crucial role in cell communication.
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Cell adhesion is particularly important in ______ tissues, where cells are tightly bound.
Cell adhesion is particularly important in ______ tissues, where cells are tightly bound.
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Cell-matrix adhesions enable cells to interact with the ______ surrounding them.
Cell-matrix adhesions enable cells to interact with the ______ surrounding them.
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Adhesion molecules allow cells to adhere to each other and the ______.
Adhesion molecules allow cells to adhere to each other and the ______.
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In connective tissues, there are few cells and a ______ amount of ECM components.
In connective tissues, there are few cells and a ______ amount of ECM components.
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Cell adhesion mechanisms are critical for the ______, development, function, and dynamics of tissues.
Cell adhesion mechanisms are critical for the ______, development, function, and dynamics of tissues.
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What is a primary role of the basal lamina?
What is a primary role of the basal lamina?
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Which of the following is NOT a feature of the extracellular matrix?
Which of the following is NOT a feature of the extracellular matrix?
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What type of chains compose the structure of laminin?
What type of chains compose the structure of laminin?
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What cellular process involves matrix metalloproteases (MMPs) during development?
What cellular process involves matrix metalloproteases (MMPs) during development?
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How do fibroblasts contribute to the extracellular matrix?
How do fibroblasts contribute to the extracellular matrix?
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What role does the extracellular matrix (ECM) play in tissues?
What role does the extracellular matrix (ECM) play in tissues?
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How do cell adhesion molecules contribute to cellular functions?
How do cell adhesion molecules contribute to cellular functions?
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What characterizes epithelial tissues in terms of cell organization?
What characterizes epithelial tissues in terms of cell organization?
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Which statement is true regarding connective tissues?
Which statement is true regarding connective tissues?
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What is a key feature of the extracellular matrix's role in cellular signaling?
What is a key feature of the extracellular matrix's role in cellular signaling?
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Which types of adhesion are primarily found in epithelial tissues?
Which types of adhesion are primarily found in epithelial tissues?
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How do cell-matrix adhesions function in connective tissues?
How do cell-matrix adhesions function in connective tissues?
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Which statement correctly describes GAGs?
Which statement correctly describes GAGs?
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What is a characteristic feature of hyaluronan?
What is a characteristic feature of hyaluronan?
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Which of the following groups is NOT a type of GAG?
Which of the following groups is NOT a type of GAG?
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What role do the highly negatively charged groups in GAGs serve?
What role do the highly negatively charged groups in GAGs serve?
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Which feature is commonly associated with all GAGs?
Which feature is commonly associated with all GAGs?
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In the context of proteoglycan synthesis, what happens to the linker added?
In the context of proteoglycan synthesis, what happens to the linker added?
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What is the primary reason for the highly extended conformation of GAGs?
What is the primary reason for the highly extended conformation of GAGs?
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Which GAG is noted for being non-sulphated?
Which GAG is noted for being non-sulphated?
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What is a common function of ECM components like fibrinogen and fibronectin?
What is a common function of ECM components like fibrinogen and fibronectin?
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What is the carbohydrate composition range of glycoproteins by weight?
What is the carbohydrate composition range of glycoproteins by weight?
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What is the primary function of collagen α-chains?
What is the primary function of collagen α-chains?
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What is a characteristic feature of fibril-associated collagens?
What is a characteristic feature of fibril-associated collagens?
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Which amino acids commonly appear in the collagen backbone structure?
Which amino acids commonly appear in the collagen backbone structure?
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What factors influence the organization of collagen fibrils in connective tissue?
What factors influence the organization of collagen fibrils in connective tissue?
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What is the approximate diameter of collagen fibrils?
What is the approximate diameter of collagen fibrils?
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What is a defining characteristic of proteoglycans compared to glycoproteins?
What is a defining characteristic of proteoglycans compared to glycoproteins?
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How do collagen trimers self-assemble?
How do collagen trimers self-assemble?
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What is the percentage of total protein mass in mammals that collagen represents?
What is the percentage of total protein mass in mammals that collagen represents?
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What role do covalent crosslinks play in collagen fibrils?
What role do covalent crosslinks play in collagen fibrils?
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What is the primary component of elastic fibers that provides resilience?
What is the primary component of elastic fibers that provides resilience?
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Which fibrous protein is specifically associated with binding type I fibrils in tendons?
Which fibrous protein is specifically associated with binding type I fibrils in tendons?
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What role does fibronectin play in the extracellular matrix?
What role does fibronectin play in the extracellular matrix?
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What structure does the basal lamina provide in tissues?
What structure does the basal lamina provide in tissues?
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Which of the following describes the structure of elastic fibers?
Which of the following describes the structure of elastic fibers?
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What characteristic of collagen fibrils contributes to their function in the body?
What characteristic of collagen fibrils contributes to their function in the body?
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What is a function of the microfibrils found within elastic fibers?
What is a function of the microfibrils found within elastic fibers?
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Which type of collagen is responsible for binding type II fibrils found in cartilage?
Which type of collagen is responsible for binding type II fibrils found in cartilage?
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How is fibronectin structured?
How is fibronectin structured?
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What is a key chemical property of elastin?
What is a key chemical property of elastin?
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Study Notes
Cell Adhesion and Cell Signalling
- Topics covered include adhesion in epithelia, the extracellular matrix, and cell-cell and cell-matrix adhesion
- Learning objectives include describing ECM components, understanding how ECM contributes to tissue structure and function, discussing adhesion molecules, understanding their role in cellular function (especially the immune system), and the role of adhesion in tissues (especially epithelia). Understanding cellular signaling with examples of pathways and components.
- Recommended textbook is Alberts et al. Molecular Biology of the Cell, Chapter 19.
- Topics for Biochemistry and Cell Biology lectures include what is the extracellular matrix?, and how do cells adhere to each other and ECM
What Holds Us Together
- Cells need to stick to each other and to other parts to form multicellular organisms.
- Cells and components are organized into tissues.
- Tissues are made of cells and extracellular space with a network of macromolecules forming the ECM
- Cell adhesion mechanisms and the ECM are crucial for tissue organization, development, function, and dynamics.
- The roles and contributions of different parts of the ECM varies in different tissue types.
Extremes of Animal Tissue Organisation
- Epithelial tissues are sheets of tightly bound cells; cell-cell adhesions are linked to the cytoskeleton, with a thin layer of ECM.
- Connective tissues are rich in components (e.g., collagen fibers), have few cells (e.g., fibroblasts, fat cells, immune cells), and prioritize cell-matrix adhesions
Fibroblasts in Rat Cornea
- Image shows fibroblasts in rat cornea.
Connective Tissue
- ECM in connective tissues determines the physical properties.
- Connective tissue provides pathways for communication and supply of blood vessels, nerves, and lymphatics.
Types of Connective Tissue
- Tendons: rope-like, high tensile strength (collagen fibrils).
- Blood vessels: resilient, flexible (elastic fibers).
- Cartilage: tensile strength and elastic properties (collagen and proteoglycan aggrecan).
- Bone: rigid and incompressible (calcified collagen).
- Vitreous content of the eye: transparent jelly (collagen fibers and hyaluronan).
- Different tissues have variants, proportions, and arrangements of similar components.
Components of the Extracellular Matrix
- Two main component types are glycosaminoglycan (GAG) polysaccharide chains, and fibrous proteins.
- GAGs include heparin sulfate, hyaluronan, proteoglycans, decorin, serglycin, perlecan, syndecan.
- Fibrous proteins include collagen, fibrillin, elastin, and laminin.
- Adhesive glycoproteins like fibrinogen, fibronectin, osteopontin, tenascin, and vitronectin are also present.
ECM Macromolecules
- Proteoglycans and GAGs are shown in an image, as are fibrous proteins, and glycoproteins.
- Hyaluronan and type IV collagen and fibrillar collagen are specific examples of components.
- Illustrations depict molecular structures, sizes, and relationships within the ECM.
GAGs
- Unbranched polysaccharide chains are composed of repeating disaccharide units.
- One sugar is an amino sugar (N-acetylglucosamine or N-acetylgalactosamine).
- The second is typically a uronic acid.
- GAGs are highly negatively charged (sulfate and carboxyl groups).
- Four main groups: hyaluronan, chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate.
Hyaluronan
- Extremely long chain length (up to 25,000 disaccharide units).
- Non-sulphated.
- Highly extended conformation.
- Attracts water, creating a non-compressible space filler.
Proteoglycan Synthesis
- Proteoglycans are synthesized in the ER and golgi and transported via the secretory pathway.
- Linkers add glycosyl transferases in ER/golgi.
- Post-translational modifications occur in the Golgi.
Examples of Proteoglycans
- Examples of proteoglycans and their properties (approximate molecular weight of core protein, type of GAG chains, number of GAG chains, location, and functions) are provided in a table, including Aggrecan, Betaglycan, Decorin, Perlecan, Syndecan-1, and Dally (Drosophila).
- Proteoglycans are a variable form of a single core protein with varying numbers of GAGS.
Aggrecan in Cartilage
- Image illustrating the structure of aggrecan and cartilage.
Rat Cartilage
- Image showing a section of rat cartilage. The structure and components are shown
Collagens
- Major fibrous ECM component, making up 25% of mammal's body protein (especially skin and bone).
- 42 human genes for collagen a-chains (form triple helix).
- Different combinations are expressed in tissues (~30 different molecules).
Collagen Fibrils in Tadpole Skin
- Image showing collagen fibrils in tadpole skin.
Some Collagens Form Fibrils
- Image showing bundles of collagen fibrils in connective tissue of embryonic chick skin.
Collagen α-chains Form Trimers
- Each chain folds into a helix with three amino acids per turn (glycine-X-Y, where X and Y are often proline and hydroxyproline).
- Chains wrap around each other to form a tightly packed triple-helical rod.
Collagen Trimers Can Form Fibrils
- Collagen trimers self-assemble into fibrils (1.5 nm diameter).
- Covalent crosslinks form between lysines and hydroxylysines (making them very strong and resistant to stretch).
- Collagen fibrils bundle into fibres.
Synthesis and Assembly of Collagen
- Steps in collagen synthesis and assembly, including pro-α-chain synthesis, hydroxylation, glycosylation, self-assembly, procollagen triple helix formation, secretion, cleavage of propeptides, self-assembly into fibrils, and aggregation to form fibers are illustrated.
Fibril-associated Collagens
- Non-helical domains interrupt triple helix to make the molecule more flexible.
- Retain propeptides so they don't aggregate into fibrils.
- Bind to fibrils to interact with other ECM molecules and determine fibril organization (e.g., type IX with II in cartilage, type XII with I in tendons).
- Images are present.
Types of Collagen and Their Properties
- Table summarizing properties (tissue distribution, polymerized form) of different collagen types, including fibril-forming and fibril-associated types. Mutant phenotypes associated with a given type of collagen (related to the structure or related disease) are also presented.
Elastic Fibres in Dog Aorta
- Images (A and B) of elastic fibers in a dog aorta, showing different magnifications.
Elastin
- Collagen fibrils provide tensile strength, but some tissues require elasticity (e.g., blood vessels, lungs, skin).
- Elastic fibers provide resilience and the ability to recoil after stretch.
- Elastin, a hydrophobic protein, is the primary component, secreted as tropoelastin and cross-linked to form a network of fibers and sheets.
- Elastic fibers are often covered with microfibrils composed of other glycoproteins (e.g., fibrillin)
Fibronectin Helps Attach Cells to the ECM
- Fibronectin forms dimers (usually heterodimers - a result of differential splicing).
- Each subunit has multiple functionally distinct domains and repeated modules (e.g., type III fibronectin repeat).
- Fibronectin can also form insoluble, crosslinked fibrils, but only when binding cells and subject to tension.
The Basal Lamina (Basement Membrane)
- Thin, tough, flexible ECM sheet.
- Essential for mechanical function (e.g., connecting epidermis to dermis).
- Underlies epithelia and surrounds muscle and nerve cells
Examples of Basal Lamina
- Examples of basal lamina in different tissue types (epithelial/luminal surface, muscle, kidney glomerulus).
- Functions such as physical support, selective cell barrier, filtration, and acting as a template for tissue regeneration, cell polarity, cell metabolism influence, and cell proliferation and differentiation are noted.
Basal Lamina in Chick Embryo Cornea
- Image showing basal lamina in chick embryo cornea.
Molecular Structure of Basal Lamina
- Diagram illustrating the arrangement of components in the basal lamina. Key components like type IV collagen, perlecan, laminin, nidogen, and integrins are presented.
Laminin Structure
- Laminin is a heterotrimer of α, β, and γ chains (multiple isoforms of each).
- Laminin has multiple binding sites for other components and cells.
- It assembles into a network via heads.
The Extracellular Matrix Is Secreted and Organized by Cells Within It
- Fibroblasts, chondroblasts (cartilage), and osteoblasts (bone) secrete and assemble ECM components (e.g., collagen fibrils).
- They bind ECM components via integrins and cytoskeleton (e.g., fibronectin fibrils).
- Cells can orient the ECM.
Remodeling/Degradation of the ECM
- Remodeling occurs during normal tissue development, wound healing, bone remodeling, cell migration (e.g., inflammation/wound healing), and tumour invasions;
- Matrix metalloproteases (MMPs) degrade ECM (e.g., MMP-9-collagenase).
- Serine proteases (e.g., urokinase-type plasminogen activator-uPA) are also involved, and are found in certain disease processes.)
- MMP activity is localized and regulated by cell-surface localization/activation from inactive precursors and inhibitors.
Dendritic Cells Use MMPs to Degrade ECM
- An image showing the action of dendritic cells using MMPs to degrade the ECM.
Roles of the ECM
- Structural integrity of connective tissues.
- Scaffold for cells.
- Reservoir for growth factors and cytokines.
- Pathways for cell migration.
- Regulation of cell shape, polarity, survival, and proliferation.
- Regulation of tissue development.
ECM Can Immobilize Chemokine Gradients
- Image shows cells migrating into skin lymphatic vessels in response to chemokine gradients.
ECM Can Immobilize Chemokine Gradients (with Heparitinase)
- Illustrative images of controlled cell migration and response to gradients.
- A graph shows the effect of hepranitinase (which degrades ECM) versus a control group on dendritic cell migration into lymphatic vessels.
Extracellular Matrix Summary
- Found in all tissues, playing a crucial structural role in connective tissues (resisting compressive forces and providing tensile strength).
- Basal lamina provides cell organization scaffolding.
- ECM comprises polysaccharides, fibrous proteins, and adhesive glycoproteins acting as adaptors.
- Components are secreted and remodeled by cells.
- Variations in their forms, amounts, and arrangement produce tissue-specific properties, and these properties greatly influence cell shape, polarity, and function and much more.
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Description
This quiz explores the critical roles of the extracellular matrix (ECM) and its components in connective tissues. It covers the structural integrity, cell organization, and various functions of the ECM, including its influence on cell behavior and tissue regeneration. Test your knowledge of ECM components and their significance in biological tissues.