Podcast
Questions and Answers
What is the primary role of the extracellular matrix in animal tissues?
What is the primary role of the extracellular matrix in animal tissues?
Which of the following cells primarily secrete the macromolecules of the extracellular matrix in connective tissues?
Which of the following cells primarily secrete the macromolecules of the extracellular matrix in connective tissues?
How does the cytoskeleton inside a cell influence the extracellular matrix outside the cell?
How does the cytoskeleton inside a cell influence the extracellular matrix outside the cell?
Which structure is formed when the extracellular matrix becomes calcified?
Which structure is formed when the extracellular matrix becomes calcified?
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What are the cells called that form cartilage in specialized connective tissues?
What are the cells called that form cartilage in specialized connective tissues?
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Which of the following describes a function of the extracellular matrix other than structural support?
Which of the following describes a function of the extracellular matrix other than structural support?
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What is a key feature of the extracellular matrix's organization?
What is a key feature of the extracellular matrix's organization?
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In addition to fibroblasts, which other cell type is specifically associated with bone formation?
In addition to fibroblasts, which other cell type is specifically associated with bone formation?
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What is the primary structural characteristic of glycosaminoglycans (GAGs)?
What is the primary structural characteristic of glycosaminoglycans (GAGs)?
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Which type of collagen is primarily found in cartilage?
Which type of collagen is primarily found in cartilage?
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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 is the primary function of elastic fibers formed by elastin?
What is the primary function of elastic fibers formed by elastin?
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Which protein comprises the major repeat domain in fibronectin?
Which protein comprises the major repeat domain in fibronectin?
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What is the distinguishing feature of fibrillar collagen?
What is the distinguishing feature of fibrillar collagen?
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What type of enzyme is a matrix metalloprotease?
What type of enzyme is a matrix metalloprotease?
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Which of the following statements about hyaluronan is true?
Which of the following statements about hyaluronan is true?
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What is the basic structure of a proteoglycan?
What is the basic structure of a proteoglycan?
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The basal lamina serves what primary purpose in tissues?
The basal lamina serves what primary purpose in tissues?
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What is necessary for fibronectin to assemble into fibrils?
What is necessary for fibronectin to assemble into fibrils?
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Which of the following statements is true about fibronectin and tension?
Which of the following statements is true about fibronectin and tension?
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What is the thickness range of the basal lamina?
What is the thickness range of the basal lamina?
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Which extracellular matrix component serves as a selective filter in the kidney glomerulus?
Which extracellular matrix component serves as a selective filter in the kidney glomerulus?
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What role do integrins play in the assembly of fibronectin fibrils?
What role do integrins play in the assembly of fibronectin fibrils?
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Which of the following components is commonly found in the basal lamina?
Which of the following components is commonly found in the basal lamina?
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How does the basal lamina influence cell behavior?
How does the basal lamina influence cell behavior?
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Where is fibronectin initially present during cell migration?
Where is fibronectin initially present during cell migration?
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What characteristic of the basal lamina is essential for all multicellular animals?
What characteristic of the basal lamina is essential for all multicellular animals?
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Which protein is indicated as forming the core protein of a proteoglycan found in the basal lamina?
Which protein is indicated as forming the core protein of a proteoglycan found in the basal lamina?
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Why does fibronectin fibril formation not occur in the bloodstream?
Why does fibronectin fibril formation not occur in the bloodstream?
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How does the basal lamina differ in its roles across various tissues?
How does the basal lamina differ in its roles across various tissues?
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What happens to type III fibronectin repeats when tension is applied?
What happens to type III fibronectin repeats when tension is applied?
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What is the primary organizing protein of the basal lamina?
What is the primary organizing protein of the basal lamina?
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Which of the following statements about laminin is correct?
Which of the following statements about laminin is correct?
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What is a consequence of mice lacking the laminin γ1 chain?
What is a consequence of mice lacking the laminin γ1 chain?
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Which type of collagen is specifically mentioned as a crucial component of the basal lamina?
Which type of collagen is specifically mentioned as a crucial component of the basal lamina?
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Which protein is involved in anchoring the basal lamina to cells?
Which protein is involved in anchoring the basal lamina to cells?
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What is the primary function of the basal lamina in tissue regeneration?
What is the primary function of the basal lamina in tissue regeneration?
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Which cells can pass through the basal lamina?
Which cells can pass through the basal lamina?
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What characteristic of type IV collagen allows it to form a flexible network in the basal lamina?
What characteristic of type IV collagen allows it to form a flexible network in the basal lamina?
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Which laminin isoform is predominantly found in skin?
Which laminin isoform is predominantly found in skin?
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How are laminins often categorized?
How are laminins often categorized?
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What disease is linked to defects in laminin-332?
What disease is linked to defects in laminin-332?
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What role do integrin family members play in the basal lamina?
What role do integrin family members play in the basal lamina?
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Which of the following is NOT a function of the basal lamina?
Which of the following is NOT a function of the basal lamina?
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Why is the basal lamina important for the epidermis?
Why is the basal lamina important for the epidermis?
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What process is used to fix and stain tissue while preventing GAG chains from collapsing?
What process is used to fix and stain tissue while preventing GAG chains from collapsing?
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What are the core proteins of proteoglycans primarily stained as in electron micrographs?
What are the core proteins of proteoglycans primarily stained as in electron micrographs?
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What is the main function of syndecans in fibroblasts?
What is the main function of syndecans in fibroblasts?
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How are collagens primarily characterized?
How are collagens primarily characterized?
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What typically provides the structure of a collagen molecule?
What typically provides the structure of a collagen molecule?
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Which type of collagen is most abundant in skin and bone?
Which type of collagen is most abundant in skin and bone?
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What structural feature do fibril-associated collagens (types IX and XII) provide?
What structural feature do fibril-associated collagens (types IX and XII) provide?
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What distinguishes type IV collagen from other types of collagen?
What distinguishes type IV collagen from other types of collagen?
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What amino acid occupies every third position in a collagen α chain?
What amino acid occupies every third position in a collagen α chain?
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How many distinct genes are there in the human genome that code for different collagen α chains?
How many distinct genes are there in the human genome that code for different collagen α chains?
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What is the typical diameter range of collagen fibrils?
What is the typical diameter range of collagen fibrils?
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What type of peptide influences cell growth and proliferation in relation to proteoglycans?
What type of peptide influences cell growth and proliferation in relation to proteoglycans?
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How do types IX and XII collagens differ from types IV and VII collagens?
How do types IX and XII collagens differ from types IV and VII collagens?
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What role does glycosylphosphatidylinositol (GPI) play in proteoglycans?
What role does glycosylphosphatidylinositol (GPI) play in proteoglycans?
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What arrangement of collagen fibrils is mainly found in tendons?
What arrangement of collagen fibrils is mainly found in tendons?
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Which property do fibril-associated collagens differ from fibrillar collagens?
Which property do fibril-associated collagens differ from fibrillar collagens?
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How do connective-tissue cells influence the organization of collagen fibrils?
How do connective-tissue cells influence the organization of collagen fibrils?
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What role does fibronectin play in collagen organization?
What role does fibronectin play in collagen organization?
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Which statement about elastic fibers is accurate?
Which statement about elastic fibers is accurate?
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What is the primary component of elastic fibers?
What is the primary component of elastic fibers?
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What feature allows elastin molecules to maintain their elastic properties?
What feature allows elastin molecules to maintain their elastic properties?
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What ensures the organization of collagen fibrils in the extracellular matrix?
What ensures the organization of collagen fibrils in the extracellular matrix?
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What is the primary function of the type III repeats found in fibronectin?
What is the primary function of the type III repeats found in fibronectin?
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Which collagen type primarily binds to type II collagen in cartilage?
Which collagen type primarily binds to type II collagen in cartilage?
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How does fibronectin form its structure?
How does fibronectin form its structure?
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What characteristic do the segments of elastin molecules possess?
What characteristic do the segments of elastin molecules possess?
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What is the function of tropoelastin in the formation of elastic fibers?
What is the function of tropoelastin in the formation of elastic fibers?
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What is the significance of the Arg-Gly-Asp (RGD) sequence in fibronectin?
What is the significance of the Arg-Gly-Asp (RGD) sequence in fibronectin?
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Which of the following statements correctly describes the splicing of fibronectin mRNA?
Which of the following statements correctly describes the splicing of fibronectin mRNA?
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What condition enhances the extensibility of elastin compared to collagen?
What condition enhances the extensibility of elastin compared to collagen?
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What is a primary difference in the structure between fibril-associated collagens and fibrillar collagens?
What is a primary difference in the structure between fibril-associated collagens and fibrillar collagens?
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What type of structure do tenascin and thrombospondin form?
What type of structure do tenascin and thrombospondin form?
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What happens to mutant mice that are unable to produce fibronectin?
What happens to mutant mice that are unable to produce fibronectin?
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Which feature contributes to the structural diversity of matrix proteins?
Which feature contributes to the structural diversity of matrix proteins?
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What is the main function of fibronectin in the extracellular matrix?
What is the main function of fibronectin in the extracellular matrix?
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Which domains in fibronectin are involved in binding to fibrin or collagen?
Which domains in fibronectin are involved in binding to fibrin or collagen?
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Which element is critical for the structural integrity of fibronectin dimers?
Which element is critical for the structural integrity of fibronectin dimers?
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Which of the following proteins contain the RGD sequence for mediating cell-surface binding?
Which of the following proteins contain the RGD sequence for mediating cell-surface binding?
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How many type III repeats are typically found in each fibronectin subunit?
How many type III repeats are typically found in each fibronectin subunit?
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Which sequence motif is crucial for tight binding to integrins?
Which sequence motif is crucial for tight binding to integrins?
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What role do the FN repeats at the N-terminus of fibronectin serve?
What role do the FN repeats at the N-terminus of fibronectin serve?
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What is the primary cellular role of integrins that bind to fibronectin?
What is the primary cellular role of integrins that bind to fibronectin?
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Which type of macromolecule is primarily responsible for forming a gel-like ground substance in connective tissue?
Which type of macromolecule is primarily responsible for forming a gel-like ground substance in connective tissue?
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What type of sugar is consistently found in the repeating disaccharide units of glycosaminoglycans?
What type of sugar is consistently found in the repeating disaccharide units of glycosaminoglycans?
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What property of glycosaminoglycans largely contributes to their ability to occupy a large amount of space within the extracellular matrix?
What property of glycosaminoglycans largely contributes to their ability to occupy a large amount of space within the extracellular matrix?
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Which of the following groups of glycosaminoglycans is characterized by having a structure that includes uronic acid?
Which of the following groups of glycosaminoglycans is characterized by having a structure that includes uronic acid?
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Which type of matrix protein is known for providing strength and organization to the extracellular matrix?
Which type of matrix protein is known for providing strength and organization to the extracellular matrix?
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What is the major functional role of glycoproteins in the extracellular matrix?
What is the major functional role of glycoproteins in the extracellular matrix?
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Which GAG is known for its abundance during tissue repair and morphogenesis?
Which GAG is known for its abundance during tissue repair and morphogenesis?
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What causes the swelling pressure or turgor that helps the matrix resist compressive forces?
What causes the swelling pressure or turgor that helps the matrix resist compressive forces?
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Which GAG is distinguished by its extensive length, up to 25,000 disaccharide units?
Which GAG is distinguished by its extensive length, up to 25,000 disaccharide units?
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Which matrix component primarily contributes to the resilience of connective tissues?
Which matrix component primarily contributes to the resilience of connective tissues?
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Which of the following best describes proteoglycans in the context of the extracellular matrix?
Which of the following best describes proteoglycans in the context of the extracellular matrix?
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What role do cations, such as Na+, play in the extracellular matrix containing GAGs?
What role do cations, such as Na+, play in the extracellular matrix containing GAGs?
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Which feature makes heparin the most densely charged biological molecule?
Which feature makes heparin the most densely charged biological molecule?
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How many main groups of glycosaminoglycans are classified based on their sugars and linkages?
How many main groups of glycosaminoglycans are classified based on their sugars and linkages?
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What role do microfibrils play in relation to elastin in the extracellular matrix?
What role do microfibrils play in relation to elastin in the extracellular matrix?
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How do fibroblasts interact with collagen in the extracellular matrix?
How do fibroblasts interact with collagen in the extracellular matrix?
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What is the consequence of mutations in the elastin gene?
What is the consequence of mutations in the elastin gene?
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Which protein is essential for the integrity of elastic fibers and binds to elastin?
Which protein is essential for the integrity of elastic fibers and binds to elastin?
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What effects can be caused by abnormal matrix density?
What effects can be caused by abnormal matrix density?
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How does the behavior of fibroblasts relate to the extracellular matrix they produce?
How does the behavior of fibroblasts relate to the extracellular matrix they produce?
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What is one of the primary functions of glycoproteins in the extracellular matrix?
What is one of the primary functions of glycoproteins in the extracellular matrix?
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What happens when fibroblasts tug on a collagen gel?
What happens when fibroblasts tug on a collagen gel?
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In which condition is the aorta prone to rupture due to structural weakness?
In which condition is the aorta prone to rupture due to structural weakness?
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What is a primary difference between the extracellular matrix in tendons and brain tissue?
What is a primary difference between the extracellular matrix in tendons and brain tissue?
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Which of the following statements is true regarding the production of collagen by fibroblasts?
Which of the following statements is true regarding the production of collagen by fibroblasts?
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What type of interaction do cells have with the extracellular matrix?
What type of interaction do cells have with the extracellular matrix?
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What role do proteoglycans play in the extracellular matrix?
What role do proteoglycans play in the extracellular matrix?
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How do fibroblast growth factors (FGFs) interact with proteoglycans?
How do fibroblast growth factors (FGFs) interact with proteoglycans?
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Which glycoprotein contributes to cell movement and organization in developing tissues?
Which glycoprotein contributes to cell movement and organization in developing tissues?
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What is the significance of the negative charges present in the extracellular matrix?
What is the significance of the negative charges present in the extracellular matrix?
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What is a characteristic feature of the elastic fibers in the extracellular matrix?
What is a characteristic feature of the elastic fibers in the extracellular matrix?
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What effect does the alignment of collagen fibers have on fibroblast behavior?
What effect does the alignment of collagen fibers have on fibroblast behavior?
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What function does type IV collagen serve in the basal lamina?
What function does type IV collagen serve in the basal lamina?
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What is one of the primary roles of fibronectin in the extracellular matrix?
What is one of the primary roles of fibronectin in the extracellular matrix?
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How do glycoproteins contribute to cell signaling?
How do glycoproteins contribute to cell signaling?
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In Drosophila, what is the consequence of a mutation in the Dally gene?
In Drosophila, what is the consequence of a mutation in the Dally gene?
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What defines the structure of glycosaminoglycan (GAG) chains?
What defines the structure of glycosaminoglycan (GAG) chains?
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Which matrix components contribute to the tensile strength of the extracellular matrix?
Which matrix components contribute to the tensile strength of the extracellular matrix?
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What role does the basal lamina serve in tissues?
What role does the basal lamina serve in tissues?
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Which of the following does NOT describe the function of the extracellular matrix?
Which of the following does NOT describe the function of the extracellular matrix?
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What is a key characteristic of the elastin molecules in the extracellular matrix?
What is a key characteristic of the elastin molecules in the extracellular matrix?
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What crucial role does the interaction of matrix components with cell-surface receptors play?
What crucial role does the interaction of matrix components with cell-surface receptors play?
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What is the primary effect of heparan sulfate chains in proteoglycans?
What is the primary effect of heparan sulfate chains in proteoglycans?
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What role does the basal lamina play in neuromuscular junction regeneration?
What role does the basal lamina play in neuromuscular junction regeneration?
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What is agrin's role in the junctional basal lamina?
What is agrin's role in the junctional basal lamina?
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What happens when a cell lacks the necessary enzymes to degrade the surrounding matrix?
What happens when a cell lacks the necessary enzymes to degrade the surrounding matrix?
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Why is matrix degradation important during tissue repair?
Why is matrix degradation important during tissue repair?
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What are matrix metalloproteases primarily responsible for?
What are matrix metalloproteases primarily responsible for?
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How do proteases ensure that matrix degradation occurs at the correct location?
How do proteases ensure that matrix degradation occurs at the correct location?
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What can occur as a result of the proteolytic cleavage of type IV collagen?
What can occur as a result of the proteolytic cleavage of type IV collagen?
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What happens to the basal lamina at the neuromuscular junction when a muscle cell is injured but not the nerve?
What happens to the basal lamina at the neuromuscular junction when a muscle cell is injured but not the nerve?
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What is the primary function of serine proteases in matrix degradation?
What is the primary function of serine proteases in matrix degradation?
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How do cell behaviors such as migration relate to matrix degradation?
How do cell behaviors such as migration relate to matrix degradation?
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Why is localized matrix degradation significant during white blood cell migration?
Why is localized matrix degradation significant during white blood cell migration?
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What happens to muscle cells in some forms of muscular dystrophy?
What happens to muscle cells in some forms of muscular dystrophy?
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What is a consequence of the lack of protease regulation in the extracellular matrix?
What is a consequence of the lack of protease regulation in the extracellular matrix?
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What unique characteristic does the synaptic region of the basal lamina possess?
What unique characteristic does the synaptic region of the basal lamina possess?
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What is the primary role of the propeptides present in pro-α chains during collagen assembly?
What is the primary role of the propeptides present in pro-α chains during collagen assembly?
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Which type of collagen is most abundant in the human body, accounting for 90% of body collagen?
Which type of collagen is most abundant in the human body, accounting for 90% of body collagen?
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What deficiency causes defective pro-α chains and results in scurvy?
What deficiency causes defective pro-α chains and results in scurvy?
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Which of the following collagens is associated with myopia and blindness?
Which of the following collagens is associated with myopia and blindness?
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How are collagen fibrils structurally strengthened after their formation?
How are collagen fibrils structurally strengthened after their formation?
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What is the function of lysyl oxidase in collagen structure?
What is the function of lysyl oxidase in collagen structure?
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Which type of collagen forms a sheet-like network in the basal lamina?
Which type of collagen forms a sheet-like network in the basal lamina?
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What consequence does impaired cross-linking of collagen have on tissues?
What consequence does impaired cross-linking of collagen have on tissues?
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What type of collagen is primarily associated with fragile skin and blood vessels prone to rupture?
What type of collagen is primarily associated with fragile skin and blood vessels prone to rupture?
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What is the main type of collagen associated with anchoring fibrils beneath stratified squamous epithelia?
What is the main type of collagen associated with anchoring fibrils beneath stratified squamous epithelia?
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Which one of the following statements about collagen types is true?
Which one of the following statements about collagen types is true?
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What happens to collagen turnover in individuals with scurvy?
What happens to collagen turnover in individuals with scurvy?
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Which type of collagen has lateral associations with type I fibrils and is involved in skeletal and muscle abnormalities?
Which type of collagen has lateral associations with type I fibrils and is involved in skeletal and muscle abnormalities?
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What condition arises from a deficiency of vitamin C affecting collagen synthesis?
What condition arises from a deficiency of vitamin C affecting collagen synthesis?
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What distinguishes hyaluronan from typical glycosaminoglycans (GAGs)?
What distinguishes hyaluronan from typical glycosaminoglycans (GAGs)?
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How is hyaluronan synthesized and released by cells?
How is hyaluronan synthesized and released by cells?
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What role does hyaluronan play during embryonic development?
What role does hyaluronan play during embryonic development?
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What happens to excess hyaluronan after cell migration has concluded?
What happens to excess hyaluronan after cell migration has concluded?
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What is a key characteristic that differentiates proteoglycans from glycoproteins?
What is a key characteristic that differentiates proteoglycans from glycoproteins?
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What is the main function of decorin within the extracellular matrix?
What is the main function of decorin within the extracellular matrix?
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Which of the following describes the properties of aggrecan?
Which of the following describes the properties of aggrecan?
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How does the structural makeup of proteoglycans contribute to their function in the extracellular matrix?
How does the structural makeup of proteoglycans contribute to their function in the extracellular matrix?
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What role does hyaluronan play in wound healing?
What role does hyaluronan play in wound healing?
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Which statement about the modification of GAGs in proteoglycans is accurate?
Which statement about the modification of GAGs in proteoglycans is accurate?
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Which of the following is NOT a feature of glycosaminoglycans (GAGs)?
Which of the following is NOT a feature of glycosaminoglycans (GAGs)?
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What enzymatic activity is responsible for linking GAG chains to their core proteins?
What enzymatic activity is responsible for linking GAG chains to their core proteins?
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Which aspect of proteoglycans facilitates their interaction with other matrix components?
Which aspect of proteoglycans facilitates their interaction with other matrix components?
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What function does the linkage tetrasaccharide serve in the synthesis of proteoglycans?
What function does the linkage tetrasaccharide serve in the synthesis of proteoglycans?
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Study Notes
Extracellular Matrix of Animals
- Tissues are composed of cells and a complex extracellular matrix (ECM)
- ECM is a network of macromolecules secreted by cells, organized in a meshwork
- ECM composition varies, allowing for diverse tissue properties (e.g., bone, teeth, cornea, tendons, jellyfish jelly, beetle/lobster carapace)
- ECM is active in regulating cell behaviors (survival, development, migration, proliferation, shape, function)
Major ECM Macromolecules
- ECM is made of three main classes of macromolecules:
- Glycosaminoglycans (GAGs): Large, highly charged polysaccharides (often covalently linked to protein as proteoglycans)
- Fibrous proteins: Primarily collagens
- Non-collagen glycoproteins: With asparagine-linked oligosaccharides
- Each tissue has a unique ECM blend for its specific needs
Glycosaminoglycans (GAGs)
- Structure: Unbranched polysaccharide chains of repeating disaccharide units (amino sugar + uronic acid, usually sulfated)
- Charge: Highly negatively charged due to sulfate and carboxyl groups
- Volume: Occupy large extracellular space due to extended conformations, forming hydrated gels
- Functions: Resist compressive forces, allow rapid diffusion of nutrients, etc.
- Types: Hyaluronan, Chondroitin sulfate, Dermatan sulfate, Heparin, Heparan sulfate, Keratan sulfate
- Defects: Can lead to genetic diseases with short stature, premature aging, and generalized defects in tissues.
Hyaluronan (Hyaluronic Acid)
- Structure: Simplest GAG, long unbranched chain, no sulfated sugars
- Synthesis: Secreted directly from cell surface by enzyme complex
- Functions: Resist compressive forces, important in tissue morphogenesis and repair. Act as a space filler for cell movements. Found in large amounts during embryonic development and wound healing.
Proteoglycans
- Structure: GAG chains covalently linked to a core protein (except hyaluronan)
- Synthesis: Core protein made by ribosomes, GAG chains assembled in Golgi
- Modifications: Sulfation and epimerization in Golgi, increase negative charge
- Diversity: Highly variable; can be large (e.g., aggrecan in cartilage) or smaller (e.g., decorin)
- Functions: Form hydrated gel, collagen embedding, cell migration/differentiation guidance, and large polymeric complexes for specific tissue properties
Collagens
- Structure: Triple-stranded helical structures of α-chains (rope-like)
- Abundance: Most abundant proteins in mammals (e.g., type I in skin, bone)
- Diversity: Over 40 types depending on combination of α-chains
- Polymerization: Form fibrils (10–300 nm diameter), bundles (collagen fibers)
- Types: Fibril-forming (type I, II, III, V), Fibril-associated (IX, XII), Network-forming (IV, VII)
- Post-translational Modifications: Hydroxylation of proline and lysine, Glycosylation, formation of triple-stranded pro-collagen (procollagen is processed), covalent cross-links, require vitamin C
- Diseases: Defects in collagen synthesis lead to conditions like osteogenesis imperfecta, vascular Ehlers-Danlos syndrome, and others.
Elastin
- Structure: Highly hydrophobic, rich in proline and glycine, not glycosylated
- Solubility/Polymerization: Soluble tropoelastin secreted extracellularly, assembled into a highly cross-linked network
- Functions: Provides elasticity to tissues (skin, blood vessels, lungs), cross-links for stiffness
- Association with Microfibrils Elastin protein is sheathed with microfibrils (e.g., fibrillin) that provide scaffolding
- Diseases: Defects lead to conditions like Marfan syndrome
Basal Lamina
- Structure: Thin, specialized ECM beneath epithelia and certain other cells
- Composition: Laminin, type IV collagen, Nidogen, Perlecan
- Functions: Mechanical support, cell adhesion, and selective barrier between cell types (like in kidneys), directs cell polarity, organization of adjacent plasma membranes, cell proliferation/differentiation, cell migration
ECM Degradation
- Degraded by proteolytic enzymes (metalloproteases, serine proteases, collagenases; need tight control)
- Crucial for tissue repair, cell division, and migration
- Important in cell movement through the ECM, and for some diseases, especially cancer
Interactions with Signal Molecules
- ECM regulates cell signaling:
- GAGs/Proteoglycans bind secreted proteins, like growth factors (fibroblast growth factors, VEGF, others), concentrate signal molecules
- Influence signaling by acting as co-receptors
- Defects in proteoglycans can alter tissue development and signaling.
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Description
This quiz explores the role and components of the extracellular matrix in animal tissues. It covers topics such as cell types associated with the extracellular matrix and its functions beyond structural support. Test your knowledge of the intricate relationships between cells and the extracellular matrix.