Extracellular Matrix and Connective Tissue 3
175 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of the following is NOT a role of the extracellular matrix?

  • Influences cell shape
  • Synthesizes proteins (correct)
  • Regulates cell behavior
  • Provides physical support

    • The extracellular matrix is produced entirely by the cells that inhabit it.

    False

    What are fibroblasts responsible for in connective tissues?

    Secreting matrix macromolecules

    Chondrocytes are specialized cells that form __________.

    <p>cartilage</p> Signup and view all the answers

    Match the cell type with the specific tissue they help form:

    <p>Fibroblasts = Connective tissue Chondrocytes = Cartilage Osteoblasts = Bone Epithelial cells = Basal lamina</p> Signup and view all the answers

    What is one function of the basal lamina?

    <p>Lies beneath epithelial cells</p> Signup and view all the answers

    The extracellular matrix can become calcified to form bone.

    <p>True</p> Signup and view all the answers

    What influence does the cytoskeleton inside a cell have on the extracellular matrix?

    <p>It controls the orientation of the matrix produced outside.</p> Signup and view all the answers

    What is the primary role of hyaluronan in tissues and joints?

    <p>Resisting compressive forces</p> Signup and view all the answers

    Hyaluronan is synthesized inside the cell and released by exocytosis.

    <p>False</p> Signup and view all the answers

    What enzyme degrades excess hyaluronan after cell migration ends?

    <p>hyaluronidase</p> Signup and view all the answers

    Hyaluronan can occupy a large volume by expanding with __________.

    <p>water</p> Signup and view all the answers

    Match the GAGs to their respective disaccharide units:

    <p>Chondroitin sulfate = D-glucuronic acid and N-acetyl-D-galactosamine Heparan sulfate = D-glucuronic acid or l-iduronic acid and N-acetyl-D-glucosamine Hyaluronan = Identical disaccharide units</p> Signup and view all the answers

    Which statement about proteoglycans is true?

    <p>They can contain up to 95% carbohydrate by mass.</p> Signup and view all the answers

    All glycoproteins contain at least one GAG chain.

    <p>False</p> Signup and view all the answers

    Which molecule helps stabilize aggrecan aggregates in cartilage?

    <p>link protein</p> Signup and view all the answers

    The repeating disaccharide sequence in hyaluronan is __________ in structure.

    <p>identical</p> Signup and view all the answers

    What type of protein is the core of a proteoglycan made by?

    <p>Membrane-bound ribosomes</p> Signup and view all the answers

    Proteoglycans are generally smaller than typical glycoproteins.

    <p>False</p> Signup and view all the answers

    What is a major role of hyaluronan during embryonic development?

    <p>Acting as a space filler</p> Signup and view all the answers

    Hyaluronan is synthesized directly from the __________ surface.

    <p>cell</p> Signup and view all the answers

    Match the following proteoglycans with their characteristic:

    <p>Aggrecan = Major component of cartilage Decorin = Binds to collagen fibrils Versican = Found in connective tissues</p> Signup and view all the answers

    Which of the following is NOT a major class of macromolecules found in the extracellular matrix?

    <p>Lipids</p> Signup and view all the answers

    Collagen fibers primarily resist compressive forces in the extracellular matrix.

    <p>False</p> Signup and view all the answers

    What is the role of glycosaminoglycans (GAGs) in connective tissue?

    <p>They form a hydrated gel that resists compressive forces and allows nutrient diffusion.</p> Signup and view all the answers

    The most densely charged biological molecule known is _____ .

    <p>heparin</p> Signup and view all the answers

    Match each group of GAGs with its primary characteristics:

    <p>Hyaluronan = Simplest GAG, repeating disaccharide units Chondroitin sulfate = Sulfo-containing GAG, involved in cartilage Heparin = Highly charged, important in blood coagulation Keratan sulfate = Found in cornea and cartilage</p> Signup and view all the answers

    Which statement best describes proteoglycans?

    <p>They are proteins bonded to GAGs.</p> Signup and view all the answers

    Hyaluronan is abundant in adult tissues but not in early embryos.

    <p>False</p> Signup and view all the answers

    How do GAG chains occupy space in the extracellular matrix?

    <p>They form hydrated gels and adopt extended conformations.</p> Signup and view all the answers

    The type of sugar found in every repeating disaccharide unit of GAGs is _____ .

    <p>amino sugar</p> Signup and view all the answers

    Match the following matrix proteins with their roles:

    <p>Collagen = Strengthens connective tissues Elastin = Provides resilience to tissues Glycoproteins = Facilitate cell migration and differentiation Proteoglycans = Form hydrated gel-like ground substance</p> Signup and view all the answers

    What is the typical weight percentage of GAGs compared to proteins in connective tissue?

    <p>Around 10%</p> Signup and view all the answers

    All tissue types contain the same composition of extracellular matrix components.

    <p>False</p> Signup and view all the answers

    What condition can arise from defects in the production of GAGs?

    <p>Short stature and skin, joint, muscle, and bone defects.</p> Signup and view all the answers

    GAGs are described as the most _____ molecules produced by animal cells.

    <p>anionic</p> Signup and view all the answers

    What is the primary purpose of the freeze substitution process?

    <p>To prevent GAG chains from collapsing</p> Signup and view all the answers

    All proteoglycans are secreted components of the extracellular matrix.

    <p>False</p> Signup and view all the answers

    Name one of the well-characterized plasma membrane proteoglycans.

    <p>Syndecan</p> Signup and view all the answers

    The core protein of syndecans interacts with the __________ cytoskeleton.

    <p>actin</p> Signup and view all the answers

    Match the collagen types with their primary functions:

    <p>Type I = Principal collagen of skin and bone Type IV = Forms part of the basal lamina Type VII = Forms anchoring fibrils Type IX = Fibril-associated collagen</p> Signup and view all the answers

    Which amino acid is found as every third amino acid in a typical collagen molecule?

    <p>Glycine</p> Signup and view all the answers

    Collagens account for approximately 25% of the total protein mass in mammals.

    <p>True</p> Signup and view all the answers

    How many distinct genes code for different collagen α chains in humans?

    <p>42</p> Signup and view all the answers

    Collagen types IX and XII are known as ___________ collagens.

    <p>fibril-associated</p> Signup and view all the answers

    What structure do Type I collagens form after being secreted into the extracellular space?

    <p>Collagen fibrils</p> Signup and view all the answers

    The extracellular domain of syndecans is never linked to GAG chains.

    <p>False</p> Signup and view all the answers

    What are the two common amino acids found in the X and Y positions of collagen sequences?

    <p>Proline and hydroxyproline</p> Signup and view all the answers

    The ___________ core protein of collagen must accommodate several amino acids to form a tight helical structure.

    <p>triple-stranded</p> Signup and view all the answers

    Which type of collagen is the principal collagen found in skin and bone?

    <p>Type I</p> Signup and view all the answers

    What length can the genes encoding the α chains of most fibrillar collagens be?

    <p>Up to 44 kilobases</p> Signup and view all the answers

    Type III collagen is primarily found in the cartilage.

    <p>False</p> Signup and view all the answers

    What is the role of vitamin C in collagen synthesis?

    <p>It is required for the hydroxylation of proline residues.</p> Signup and view all the answers

    A deficiency in vitamin C can lead to __________, characterized by fragile blood vessels and poor wound healing.

    <p>scurvy</p> Signup and view all the answers

    Match the collagen types with their corresponding characteristics:

    <p>Type I = Bone, skin, tendons Type II = Cartilage, intervertebral disc Type III = Blood vessels, skin Type IV = Basal lamina structure</p> Signup and view all the answers

    What is the polymerized form of Type I collagen?

    <p>Fibril</p> Signup and view all the answers

    Propeptides in pro-α chains are removed before the chains enter the endoplasmic reticulum.

    <p>False</p> Signup and view all the answers

    What is the primary function of hydroxylation in collagen synthesis?

    <p>To stabilize the triple-helical structure of collagen.</p> Signup and view all the answers

    After secretion, procollagen molecules are converted to collagen through the removal of __________.

    <p>propeptides</p> Signup and view all the answers

    Which type of collagen is associated with the formation of anchoring fibrils?

    <p>Type VII</p> Signup and view all the answers

    Collagen fibrils can resist compressive forces effectively.

    <p>False</p> Signup and view all the answers

    What structures are formed through covalent cross-linking of collagen molecules?

    <p>Collagen fibrils.</p> Signup and view all the answers

    Match the collagen types with their associated mutant phenotypes:

    <p>Type I = Osteogenesis imperfecta Type II = Chondrodysplasia Type III = Vascular Ehlers–Danlos syndrome Type IV = Kidney disease</p> Signup and view all the answers

    What happens to collagen production in the case of scurvy?

    <p>Collagen production is inhibited</p> Signup and view all the answers

    The enzyme __________ is key to forming covalent cross-links in collagen.

    <p>lysyl oxidase</p> Signup and view all the answers

    In which type of tissue are collagen fibrils organized in parallel bundles aligned along the major axis of tension?

    <p>Tendons</p> Signup and view all the answers

    Elastic fibers in tissues like skin and blood vessels are mainly composed of collagen.

    <p>False</p> Signup and view all the answers

    What is the role of fibronectin in collagen fibril organization?

    <p>It helps guide the organization of collagen fibrils.</p> Signup and view all the answers

    Collagen fibrils are arranged in __________ layers in the cornea.

    <p>plywoodlike</p> Signup and view all the answers

    Match the type of collagen with its associated tissue or function:

    <p>Type I = Tendons and various other tissues Type II = Cartilage Type IX = Cornea and vitreous of the eye Type XII = Tendons</p> Signup and view all the answers

    What characterizes the segments of elastin in elastic fibers?

    <p>They are predominantly hydrophobic.</p> Signup and view all the answers

    Collagen fibrils do not have varying arrangements in different tissues.

    <p>False</p> Signup and view all the answers

    What is the significance of the random-coil conformation in elastin molecules?

    <p>It allows the network to stretch and recoil like a rubber band.</p> Signup and view all the answers

    The main component of elastic fibers is __________.

    <p>elastin</p> Signup and view all the answers

    Match the following collagen types with their specific characteristics:

    <p>Type IX = Binds to type II collagen fibrils Type XII = Binds to type I collagen fibrils Fibrillar collagens = Form fibrils in the extracellular matrix Fibril-associated collagens = Do not aggregate to form fibrils</p> Signup and view all the answers

    How do cells regulate the organization of collagen fibrils after secretion?

    <p>By guiding collagen fibril formation near the plasma membrane.</p> Signup and view all the answers

    Elastic fibers are less extensible than rubber bands of the same cross-sectional area.

    <p>False</p> Signup and view all the answers

    What is the relationship between collagen fibrils and elastin in connective tissues?

    <p>Collagen fibrils limit stretching and prevent tearing of tissues with elastin.</p> Signup and view all the answers

    The cells that produce collagen fibrils can express different types of __________ collagens.

    <p>fibrillar</p> Signup and view all the answers

    Which type of repeat is the major repeat domain in fibronectin?

    <p>Type III fibronectin repeat</p> Signup and view all the answers

    Fibronectin is found only in mammals.

    <p>False</p> Signup and view all the answers

    What is the consequence of mutant mice lacking fibronectin?

    <p>They die early in embryogenesis due to improper blood vessel formation.</p> Signup and view all the answers

    Fibronectin forms _______ linked at the C-termini.

    <p>dimers</p> Signup and view all the answers

    What does the Arg-Gly-Asp (RGD) sequence do in fibronectin?

    <p>Mediates cell-surface binding</p> Signup and view all the answers

    Fibronectin can form multiple isoforms through alternative splicing.

    <p>True</p> Signup and view all the answers

    Name one protein besides fibronectin that contains an RGD sequence.

    <p>Thrombospondin</p> Signup and view all the answers

    The defects in endothelial cell formation in mutant mice are thought to result from abnormalities in their interactions with the surrounding __________.

    <p>extracellular matrix</p> Signup and view all the answers

    What is one of the key functions of fibronectin in the body?

    <p>Facilitating cell-matrix interactions</p> Signup and view all the answers

    Match the fibronectin segments with their binding sites:

    <p>Type III repeat = Integrin binding N-terminus = Collagen binding Adjacent type III repeats = Heparin binding Another segment = Proteoglycan binding</p> Signup and view all the answers

    What is the primary component of the extracellular matrix in arteries?

    <p>Elastin</p> Signup and view all the answers

    Fibronectin is made up of a single polypeptide chain.

    <p>False</p> Signup and view all the answers

    Mutations in the elastin gene can lead to the narrowing of the aorta and excessive proliferation of smooth muscle cells.

    <p>True</p> Signup and view all the answers

    How many exons does the fibronectin gene contain?

    <p>About 50 exons</p> Signup and view all the answers

    The ________ structure of fibronectin is essential for its multifunctionality.

    <p>dimeric</p> Signup and view all the answers

    What role do microfibrils play in relation to elastin?

    <p>They provide scaffolding to guide elastin deposition.</p> Signup and view all the answers

    Mutations in the fibrillin gene can cause __________ syndrome.

    <p>Marfan</p> Signup and view all the answers

    Which extracellular protein is known to use a similar RGD sequence strategy to cause bleeding?

    <p>Disintegrins</p> Signup and view all the answers

    What type of repeat domains are found in many matrix proteins that resemble those in fibronectin?

    <p>Epidermal growth factor (EGF) repeats</p> Signup and view all the answers

    Match the following components of the extracellular matrix with their functions:

    <p>Elastin = Provides elasticity Collagen = Offers structural support Fibronectin = Binds cells to the matrix Fibrillin = Essential for elastic fiber integrity</p> Signup and view all the answers

    How do fibroblasts influence the extracellular matrix?

    <p>By organizing collagen fibers</p> Signup and view all the answers

    Abnormally high matrix density is associated with better health outcomes.

    <p>False</p> Signup and view all the answers

    What happens to a collagen gel when fibroblasts pull on it?

    <p>It contracts to a small fraction of its initial volume.</p> Signup and view all the answers

    Arrays of microfibrils persist in the absence of elastin and are important for holding the __________ in place in the eye.

    <p>lens</p> Signup and view all the answers

    Match the following tissue types with their composition:

    <p>Tendons = Dense matrix Cartilage = Rigid matrix Fat = Soft elastic matrix Brain = Soft elastic matrix</p> Signup and view all the answers

    Which of the following is a function of glycoproteins in the extracellular matrix?

    <p>Organize the matrix and help cells attach</p> Signup and view all the answers

    The mechanical properties of the extracellular matrix do not influence the behavior of surrounding cells.

    <p>False</p> Signup and view all the answers

    What is one significant effect of fibroblasts on collagen fibers?

    <p>They influence the alignment of collagen fibers.</p> Signup and view all the answers

    The presence of specific __________ in different tissues determines the overall density and composition of the extracellular matrix.

    <p>cells</p> Signup and view all the answers

    Which of the following is a type of glycosaminoglycan that is not sulfated?

    <p>Hyaluronan</p> Signup and view all the answers

    Fibronectin is a protein that helps bind cells to the extracellular matrix.

    <p>True</p> Signup and view all the answers

    What type of collagen is primarily found in cartilage?

    <p>Type II collagen</p> Signup and view all the answers

    The tripeptide sequence __________ serves as a binding site for integrins.

    <p>RGD</p> Signup and view all the answers

    Match the following types of collagen with their primary locations:

    <p>Type I = Skin, tendon, and bone Type II = Cartilage Type IV = Basal laminae Type III = Reticular fibers in organs</p> Signup and view all the answers

    Which protein forms extensible fibers in connective tissues?

    <p>Elastin</p> Signup and view all the answers

    The RGD sequence is found exclusively in collagen proteins.

    <p>False</p> Signup and view all the answers

    Name one function of the basal lamina.

    <p>Separates epithelial sheets from connective tissue</p> Signup and view all the answers

    The major repeat domain in fibronectin is known as the type III fibronectin __________.

    <p>repeat</p> Signup and view all the answers

    Which enzyme is known to degrade matrix proteins in the extracellular matrix?

    <p>Matrix metalloprotease</p> Signup and view all the answers

    What primarily regulates the assembly of fibronectin fibrils?

    <p>Tension exerted by cells</p> Signup and view all the answers

    Fibronectin molecules can self-assemble into fibrils in a test tube without cellular interaction.

    <p>False</p> Signup and view all the answers

    What are integrins, and what role do they play in fibronectin assembly?

    <p>Integrins are proteins that link fibronectin outside the cell to the actin cytoskeleton inside the cell, transmitting tension that aids in fibril assembly.</p> Signup and view all the answers

    The basal lamina is an essential underpinning of all __________.

    <p>epithelia</p> Signup and view all the answers

    Match the cellular component with its role in the basal lamina:

    <p>Laminin = Supports cell adhesion Type IV Collagen = Provides structural support Nidogen = Links other components Perlecan = Acts as a proteoglycan</p> Signup and view all the answers

    How thick is the basal lamina typically?

    <p>40–120 nm</p> Signup and view all the answers

    The basal lamina only plays a structural role within tissues.

    <p>False</p> Signup and view all the answers

    Name one function of the basal lamina besides providing structural support.

    <p>It influences cell metabolism.</p> Signup and view all the answers

    Fibronectin plays a role in forming __________ where there is a mechanical need.

    <p>fibrils</p> Signup and view all the answers

    Match the cellular component to its description:

    <p>Fibronectin = A glycoprotein that helps form fibrils Integrin = Protein that links the extracellular matrix to the cytoskeleton Collagen = Protein primarily providing tensile strength in tissues Laminin = Glycoprotein enriching the basal lamina</p> Signup and view all the answers

    Which of the following is NOT a component of the basal lamina?

    <p>Hyaluronic acid</p> Signup and view all the answers

    Fibronectin is only found in its soluble form within the bloodstream.

    <p>False</p> Signup and view all the answers

    What role does stretching have on the fibers of fibronectin?

    <p>Stretching exposes cryptic binding sites in fibronectin, promoting fibril formation.</p> Signup and view all the answers

    The basal lamina participates in __________ by serving as a highway for cell movement.

    <p>cell migration</p> Signup and view all the answers

    What is the primary role of laminin in the basal lamina?

    <p>Organizing the sheet structure</p> Signup and view all the answers

    The basal lamina prevents all types of immune cells from passing through its barrier.

    <p>False</p> Signup and view all the answers

    What happens to mice that lack the laminin γ1 chain?

    <p>They die during embryogenesis due to inability to form a basal lamina.</p> Signup and view all the answers

    The basal lamina can act as a selective barrier to the movement of __________.

    <p>cells and molecules</p> Signup and view all the answers

    Which of the following components is NOT part of the basal lamina?

    <p>Fibroblast growth factor</p> Signup and view all the answers

    Type IV collagen molecules form a rigid structure in the basal lamina.

    <p>False</p> Signup and view all the answers

    What is a characteristic feature of the structure of laminins?

    <p>They are composed of three long polypeptide chains arranged in an asymmetric bouquet-like shape.</p> Signup and view all the answers

    In people with genetic defects in laminin-332, the condition known as __________ occurs.

    <p>junctional epidermolysis bullosa</p> Signup and view all the answers

    Match the following laminin isoforms with their respective tissue distribution:

    <p>Laminin-332 = Skin Laminin-211 = Muscle Laminin-411 = Endothelial cells Laminin-111 = Various tissues</p> Signup and view all the answers

    Which protein interacts with laminin to aid in the assembly of the basal lamina?

    <p>Integrin</p> Signup and view all the answers

    The basal lamina plays a role in tissue regeneration after injury.

    <p>True</p> Signup and view all the answers

    What is the role of nidogen in the basal lamina?

    <p>Nidogen helps to cross-link laminin and type IV collagen, stabilizing the structure.</p> Signup and view all the answers

    Laminins are held together by __________ bonds.

    <p>disulfide</p> Signup and view all the answers

    Match the component of the basal lamina with its description:

    <p>Type IV collagen = Creates a flexible, felt-like network Laminin = Organizes the sheet structure Nidogen = Cross-links other proteins Perlecan = Provides binding sites for growth factors</p> Signup and view all the answers

    What is the primary function of matrix proteoglycans?

    <p>To regulate the distribution and activity of secreted proteins</p> Signup and view all the answers

    The basal lamina is a type of extracellular matrix found under all cell types.

    <p>False</p> Signup and view all the answers

    Name one function of the extracellular matrix.

    <p>Provides a scaffold for tissue structure</p> Signup and view all the answers

    Fibroblast growth factors (FGFs) interact with __________ to enhance their activity.

    <p>proteoglycans</p> Signup and view all the answers

    Match the following matrix molecules with their functions:

    <p>Collagen = Provides tensile strength Elastin = Offers elasticity Fibronectin = Binds to integrins and promotes adhesion Laminin = Contributes to the structure of the basal lamina</p> Signup and view all the answers

    Which signal molecule is helped by proteoglycans in generating morphogen gradients?

    <p>Dpp</p> Signup and view all the answers

    Glycosaminoglycans (GAGs) are covalently linked to proteins to form glycoproteins.

    <p>False</p> Signup and view all the answers

    What role do cell-surface receptors play in relation to proteoglycans?

    <p>They interact with proteoglycans to facilitate signaling.</p> Signup and view all the answers

    Proteoglycans provide a dense array of __________-binding sites, limiting the diffusion of secreted factors.

    <p>growth factor</p> Signup and view all the answers

    Match the following roles with the corresponding extracellular matrix components:

    <p>Type IV collagen = Forms a mesh in the basal lamina Elastin = Provides elasticity Fibronectin = Promotes cell attachment Heparan sulfate = Binds growth factors</p> Signup and view all the answers

    What can occur if specific proteoglycans are mutated?

    <p>Severe developmental defects</p> Signup and view all the answers

    Collagen provides strength and resilience to the extracellular matrix.

    <p>True</p> Signup and view all the answers

    What is a major component of the basal lamina?

    <p>Laminin</p> Signup and view all the answers

    The extracellular matrix affects cell behavior by influencing cell __________ and differentiation.

    <p>polarity</p> Signup and view all the answers

    What is the role of the basal lamina in the neuromuscular junction?

    <p>It facilitates the chemical synapse between neurons and muscle cells.</p> Signup and view all the answers

    Matrix metalloproteases play a key role in the degradation of the extracellular matrix.

    <p>True</p> Signup and view all the answers

    What molecule do motor neuron axons deposit in the junctional basal lamina?

    <p>Agrin</p> Signup and view all the answers

    The two general classes of proteases involved in matrix degradation are _______ and serine proteases.

    <p>matrix metalloproteases</p> Signup and view all the answers

    Match the following components with their associated roles in the extracellular matrix:

    <p>Collagen = Provides tensile strength Laminin = Influences cell adhesion Fibronectin = Guides cell movement Agrin = Regulates receptor clustering</p> Signup and view all the answers

    What is required for cells to divide while embedded in matrix?

    <p>Localized degradation of matrix components</p> Signup and view all the answers

    Cleavage of type IV collagen always leads to its complete destruction.

    <p>False</p> Signup and view all the answers

    Which process involves the continual turnover of extracellular matrix macromolecules?

    <p>Remodeling</p> Signup and view all the answers

    During muscle regeneration, the junctional basal lamina causes new acetylcholine receptors to accumulate at the original _______ site.

    <p>synaptic</p> Signup and view all the answers

    What happens to the matrix during tissue repair?

    <p>It is rapidly degraded and resynthesized.</p> Signup and view all the answers

    Defects in basal lamina components can lead to muscular dystrophy.

    <p>True</p> Signup and view all the answers

    What is a consequence of a cell lacking the enzymes needed to degrade the surrounding matrix?

    <p>It is inhibited from dividing.</p> Signup and view all the answers

    Proteases that have a reactive _____ in their active site are known as serine proteases.

    <p>serine</p> Signup and view all the answers

    Match the following methods of matrix regulation with their description:

    <p>Anchoring proteins = Confine protease activity to cell surface Membrane-associated activators = Activate proteases on demand Protease inhibitors = Prevent unwanted degradation Proteolytic cleavage = Releases biologically active fragments</p> Signup and view all the answers

    What distinguishes the synaptic region of the basal lamina?

    <p>It contains unique isoforms of type IV collagen and laminin.</p> Signup and view all the answers

    Study Notes

    Extracellular Matrix of Animals

    • The extracellular matrix (ECM) is a complex network of macromolecules outside cells, consisting of proteins and polysaccharides.
    • Functions of ECM: Provides physical support, regulates cell behavior (survival, migration, proliferation, shape, and function), and influences tissue development and morphogenesis.
    • Major classes of ECM macromolecules:
      • Glycosaminoglycans (GAGs): Highly charged polysaccharides, typically linked to proteins as proteoglycans.
      • Fibrous proteins: Mainly collagens that provide tensile strength and structural integrity.
      • Non-collagen glycoproteins: Diverse group that mediates cell adhesion, migration, and signaling.
    • ECM is produced and organized by cells:
      • Fibroblasts: Primary producers of ECM in most connective tissues.
      • Chondrocytes: Secrete ECM for cartilage formation.
      • Osteoblasts: Secrete ECM for bone formation.
      • Cell cytoskeleton: Influences the orientation of the matrix produced outside the cell.

    Glycosaminoglycans (GAGs)

    • GAGs: Unbranched polysaccharide chains with repeating disaccharide units, usually sulfated and negatively charged.
    • Types of GAGs: Hyaluronan, chondroitin sulfate/dermatan sulfate, heparin/heparan sulfate, and keratan sulfate.
    • Properties of GAGs:
      • Highly hydrophilic: Attract large amounts of water, forming hydrated gels even at low concentrations.
      • Resist compressive forces: Contribute to turgor pressure in tissues like cartilage.
    • Defects in GAG production: Can affect multiple body systems, as seen in certain rare genetic diseases.

    Hyaluronan

    • Simplest form of GAG: Repeating disaccharide units, no sulfated sugars.
    • Found in all tissues and fluids: Abundant during embryonic development.
    • Functions:
      • Space filler during morphogenesis and tissue repair.
      • Drives formation of structures in the developing heart (valves and septa).
      • Lubicant in joint fluid.

    Proteoglycans

    • GAGs are attached to proteins as proteoglycans: Core protein with covalently linked GAG chains.
    • Synthesized in ER and Golgi: GAG chains are assembled on the core protein, undergoing modifications like sulfation.
    • Heterogeneous: Can vary in number and type of GAG chains on a single core protein.
    • Examples:
      • Aggrecan: Large proteoglycan in cartilage, forms aggregates with hyaluronan.
      • Decorin: Smaller proteoglycan, binds to collagen fibrils, regulates fibril assembly.
    • Functions:
      • Hydration and resistance to compression: Similar to GAGs.
      • Interaction with other components: Bind to fibrous matrix proteins, forming complex assemblies.
    • Plasma membrane proteoglycans:
      • Syndecans: Integral membrane proteoglycans, interact with the actin cytoskeleton and signaling molecules.
      • Glypicans: GPI-anchored proteoglycans, involved in growth factor signaling.

    Collagens

    • Most abundant protein in mammals: Essential for structure and integrity of tissues.
    • Triple-stranded helical structure: Three α chains wound together.
    • Rich in proline and glycine: Essential for helix formation.
    • Types of collagen:
      • Fibril-forming collagens: Type I (skin and bone) assemble into collagen fibrils.
      • Fibril-associated collagens: Types IX and XII, decorate the surface of collagen fibrils.
      • Network-forming collagens: Type IV (basal lamina) and type VII (anchoring fibrils).
      • Collagen-like proteins: Contain short collagen-like segments.
    • Functions:
      • Tensile strength: Resist stretching forces.
      • Structural support: Provide framework for tissues.
      • Cell adhesion: Interact with other ECM components and cells.

    Collagen Types

    • Collagen is a family of fibrous proteins
    • Collagen type XVII is a transmembrane collagen found in hemidesmosomes
    • Collagen type XVIII is a proteoglycan core protein found in the basal lamina
    • Many collagens are encoded by genes with multiple exons, often with a repeating 54-nucleotide pattern, suggesting a common ancestral gene

    ### Collagen Types and Their Properties

    • Type I collagen is the most abundant collagen type, found in bone, skin, tendons, and ligaments
    • Mutations in type I collagen can cause osteogenesis imperfecta, leading to bone defects and fractures
    • Type II collagen is found in cartilage and contributes to its structural integrity
    • Mutations in type II collagen can cause chondrodysplasia, resulting in cartilage deficiency and dwarfism
    • Type III collagen is abundant in skin, blood vessels, and internal organs, providing elasticity and strength
    • Mutations in type III collagen are associated with vascular Ehlers–Danlos syndrome, leading to fragile skin, loose joints, and prone-to-rupture blood vessels
    • Type IV collagen forms sheet-like networks in the basal lamina
    • Mutations in type IV collagen can cause kidney disease (glomerulonephritis) and deafness.

    Collagen Synthesis and Assembly

    • Individual collagen polypeptide chains are synthesized on membrane-bound ribosomes and injected into the ER lumen as precursor pro-α chains
    • These precursors have propeptides at both the N- and C-terminal ends
    • Selected prolines and lysines in the ER lumen are hydroxylated to form hydroxyproline and hydroxylysine
    • Some hydroxylysines are then glycosylated
    • Three pro-α chains assemble to form a triple-stranded, helical molecule known as procollagen
    • The hydroxyl groups of hydroxyproline and hydroxylysine form interchain hydrogen bonds, stabilizing the triple helix
    • Proline hydroxylation requires ascorbic acid (vitamin C)
    • In scurvy (vitamin C deficiency), defective pro-α chain assembly results in collagen fibril formation inhibition
    • After secretion, propeptides are removed by proteolytic enzymes, converting procollagen to collagen
    • Collagen molecules assemble in the extracellular space to form larger fibrils
    • Collagen fibrils are cross-linked by covalent bonds between lysine residues, providing tensile strength
    • Cross-linking is crucial for tissue strength, as seen in the Achilles tendon
    • The extent and type of cross-linking vary depending on the tissue

    Other Collagen Types

    • Fibril-associated collagens, such as types IX and XII, help organize collagen fibrils
    • Type IX collagen binds to type II collagen fibrils in cartilage, cornea, and vitreous humor.
    • Type XII collagen binds to type I collagen fibrils in tendons and other tissues
    • They have a more flexible triple-stranded helical structure due to short nonhelical domains
    • They associate with fibrils in a periodic manner rather than forming their own fibrils.

    Elastin

    • Elastin is a hydrophobic protein rich in proline and glycine, giving tissues elasticity
    • Elastin is not glycosylated
    • Soluble tropoelastin is secreted and assembled into elastic fibers
    • Elastin molecules are cross-linked, generating a network of fibers and sheets
    • Elastin is composed of alternating hydrophobic segments (for elasticity) and α-helical segments (for cross-linking)
    • Elastin fibers contribute to the elasticity of skin, blood vessels, and lungs.
    • Elastin deficiency can lead to narrowing of blood vessels and smooth muscle cell proliferation

    ### Microfibrils

    • Microfibrils are composed of glycoproteins, including fibrillin
    • They form a sheath around elastin fibers
    • They provide scaffolding for elastin deposition and contribute to tissue elasticity.
    • Mutations in the fibrillin gene cause Marfan syndrome, characterized by aortic aneurysms, lens displacement, and skeletal abnormalities.

    Cell-Matrix Interactions

    • Cells interact with the extracellular matrix mechanically and chemically
    • Fibroblasts can reorganize the extracellular matrix in culture by pulling on collagen fibers
    • They can align collagen fibers and deposit them in specific orientations
    • They also regulate matrix density and composition by adjusting collagen and other protein production rates
    • Matrix density influences cell behavior, such as proliferation and migration

    Fibronectin

    • Fibronectin is a multidomain glycoprotein important for cell-matrix interactions
    • It binds to other matrix macromolecules and cell surface receptors
    • It helps organize the matrix and guide cell movements
    • It can bind and regulate peptide growth factors.

    Fibronectin

    • Fibronectin is a dimer composed of two large subunits joined by disulfide bonds
    • Each subunit contains several domains
    • It is encoded by only one gene in the genome
    • The gene has 50 exons
    • Some exons can be spliced differently to produce multiple isoforms
    • One region of fibronectin binds to collagen, another to proteoglycans, and another to specific integrins on the surface of various types of cells
    • Fibronectin can exist both in a soluble form and as insoluble fibronectin fibrils
    • Fibrils are cross-linked to one another by disulfide bonds
    • Cells assemble fibrils through integrins
    • Integrins connect fibronectin outside the cell to the actin cytoskeleton inside the cell
    • This linkage transmits tension to the fibronectin molecules and stretches them, exposing cryptic binding sites

    Basal Lamina

    • The basal lamina is a thin, tough, flexible sheet of extracellular matrix
    • It is essential for all epithelia
    • It lies beneath epithelial cells and also surrounds individual muscle cells, fat cells, and Schwann cells
    • The basal lamina separates these cells and epithelia from the underlying connective tissue
    • Major components of the basal lamina are laminin, type IV collagen, nidogen, and perlecan
    • Laminin is a large family of proteins with each member composed of three long polypeptide chains
    • Laminin molecules self-assemble into a network
    • Type IV collagen molecules assemble into a flexible, felt-like network
    • The basal lamina is synthesized by the cells on each side of it
    • Laminin molecules are primarily organized by cell-surface integrins
    • Interactions between laminin and cell-surface receptors are critical for adhesion of epithelia to the underlying connective tissue

    Matrix Degradation

    • Cells can also degrade the extracellular matrix
    • Matrix degradation is required for processes such as tissue repair and remodeling
    • Cells need enzymes to degrade the surrounding matrix in order to divide and migrate
    • Localized degradation is required for cells to escape from confinement by a basal lamina
    • Matrix degradation is also important for the spread of cancer cells
    • Matrix components are degraded by extracellular proteolytic enzymes (proteases)

    Extracellular Matrix

    • Cells are embedded in an intricate extracellular matrix.
    • The matrix is a complex meshwork of macromolecules, and is responsible for:
      • Holding cells together
      • Influencing cell survival, development, shape, polarity and migratory behavior

    Extracellular Matrix Composition

    • The extracellular matrix contains various protein fibers interwoven in a network of glycosaminoglycan (GAG) chains.
      • GAGs are negatively charged polysaccharide chains covalently linked to protein to form proteoglycan molecules.
      • GAGs attract water and occupy a large volume of extracellular space.
      • GAGs can either be part of the extracellular matrix or be found on the surface of cells, where they function as co-receptors for secreted signal proteins.
    • Fiber-forming proteins give the matrix strength and resilience.
      • Fibrillar collagens are rope-like, triple-stranded helical molecules that aggregate into long fibrils in the extracellular space.
        • Providing tensile strength.
        • Forming structures to which cells can be anchored.
      • Elasticity is provided by elastin molecules, which form an extensive cross-linked network of fibers and sheets that can stretch and recoil.

    Basal Lamina

    • A specialized form of extracellular matrix that underlies epithelial cells or is wrapped around other cell types, such as muscle cells.
    • Basal lamina composition:
      • Laminin molecules linked together by their side-arms
      • Type IV collagen molecules together with the protein nidogen and the large proteoglycan perlecan
    • Basal lamina function:
      • Provides mechanical support for epithelia.
      • Forms the interface and attachment between epithelia and connective tissue.
      • Serves as filters in the kidney.
      • Acts as barriers to keep cells in their proper compartments.
      • Influences cell polarity and cell differentiation.
      • Guides cell migration during development and tissue regeneration.

    Matrix Proteases

    • Matrix metalloproteases are Ca2+ or Zn2+ dependent proteolytic enzymes in the extracellular matrix that degrade matrix proteins.
    • Serine proteases have a reactive serine in their active site.
    • Metalloproteases and serine proteases cooperate to degrade matrix proteins like collagen, laminin and fibronectin.
      • Some are highly specific, cleaving particular proteins at a small number of sites, ensuring the structural integrity of the matrix is maintained.
      • Others are less specific, but act where they are needed and are crucial for a cell’s ability to divide when embedded in the matrix.
    • Protease activity is tightly controlled to prevent the collapse of the body's fabric.
    • Control mechanisms involve:
      • Specific anchoring proteins
      • Membrane-associated activators
      • Specific protease inhibitors in regions where protease activity is not needed.

    Matrix Degradation and Biological Activity

    • The proteolytic cleavage of matrix proteins does not always lead simply to their destruction.
    • In some cases, protein fragments with specific biological activities are generated.
      • Cleavage of type IV collagen by matrix metalloproteases leads to the release of protein fragments that inhibit the local formation of blood vessels.
      • Cleavage of laminin in certain tissues can generate protein fragments that help govern local cell proliferation.

    Proteoglycans and Glycoproteins Regulation of Secreted Proteins

    • The extracellular matrix also influences cell signaling.
    • Cells communicate with each other by secreting peptide signal molecules like growth factors and morphogens, which diffuse through the extracellular fluid to influence other cells.
    • The extracellular matrix, with its high density of negative charges and protein-interaction domains, can interact with the signal molecules, altering their function in a variety of ways.
    • Proteoglycans:
      • Highly charged heparan sulfate chains
      • Interact with secreted signal molecules, including FGFs and VEGF, which stimulate a variety of cell types to proliferate.
      • Thought to generate large local reservoirs of these factors, limiting their diffusion and focusing their actions on nearby cells.
      • Might help generate steep morphogen gradients in an embryo, important in the patterning of tissues during development.
    • FGF Activity can also be enhanced by proteoglycans, which oligomerize the FGF molecules and also interact with cell-surface FGF receptors, enabling the FGF to cross-link and activate its receptors more effectively.
    • Proteoglycan Inactivation: Severe developmental defects can occur when specific proteoglycans are inactivated by mutation.
      • For example, in Drosophila, several signal proteins’ functions during development depend on interactions with the membrane-associated proteoglycans Dally and Dally-like.
    • Other matrix molecules that interact with signal proteins include:
      • Type IV collagen of the basal lamina interacts with Dpp in Drosophila.
      • Fibronectin contains a type III fibronectin repeat that interacts with VEGF and another domain that interacts with hepatocyte growth factor (HGF).
    • Matrix glycoproteins contain extensive arrays of binding domains that influence the presentation of signal proteins to their target cells.
    • Many matrix glycoproteins contain domains that bind directly to specific cell-surface receptors, thereby generating signals that influence the behavior of the cells.

    Summary

    • Cells are embedded in an intricate extracellular matrix.
    • The matrix is responsible for holding cells together and influencing cell survival, development, shape, polarity and migratory behavior.
    • The matrix consists of protein fibers and GAG chains.
    • Fibrillar collagens provide tensile strength, while elastin molecules provide elasticity.
    • The basal lamina is a specialized form of extracellular matrix that underlies epithelial cells or is wrapped around other cell types, such as muscle cells.
    • Matrix metalloproteases and serine proteases degrade matrix proteins, playing a crucial role in cell migration and division.
    • Proteoglycans act as regulators of the distribution and activity of signal molecules.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Description

    Test your knowledge on the functions and roles of the extracellular matrix and its cell types. This quiz covers fibroblasts, chondrocytes, and the basal lamina, as well as their contributions to various connective tissues. Challenge yourself with matching questions and true/false statements about this vital component of tissue structure.

    More Like This

    Connective Tissue Extracellular Matrix
    11 questions

    Connective Tissue Extracellular Matrix

    CaptivatingSeaborgium avatar
    CaptivatingSeaborgium
    Connective Tissue and Extracellular Matrix Quiz
    18 questions

    Connective Tissue and Extracellular Matrix Quiz

    SecureHarpGuitar avatar
    SecureHarpGuitar
    Connective Tissue and Extracellular Matrix
    8 questions

    Connective Tissue and Extracellular Matrix

    EnterprisingJasper6752 avatar
    EnterprisingJasper6752
    Types of Connective Tissue Cells
    10 questions

    Types of Connective Tissue Cells

    BestPerformingBlue7038 avatar
    BestPerformingBlue7038
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser