Biochemistry of Extracellular Matrix

Extracellular Matrix (ECM)

• ECM is a complex network of proteins and carbohydrates that provides structural support, maintains tissue architecture, and regulates various cellular functions
• Composition of ECM varies in different tissues, depending on their functions
• ECM protects organs, provides elasticity, and keeps cells, large molecules, and microorganisms in place
• ECM also provides a porous pathway for the diffusion of nutrients and oxygen to individual cells

Collagen

• Collagen is the most abundant fibrous protein in the human body (~25% of all proteins)
• Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
• Collagen is composed of three α-chains, each approximately 1000 amino acids long, with a repeating pattern of Gly-X-Y
• Hydroxyproline and hydroxylysine are essential for collagen stability and cross-linking
• Collagen triple helix is a rod-like molecule, 300 nm long and 1.5 nm thick, with a molecular weight of 300 kDa
• Collagen has high tensile strength due to its unique structure and cross-linking

Collagen Synthesis and Modification

• Collagen synthesis occurs intracellularly, with post-translational modifications such as hydroxylation and glycosylation
• Procollagen is converted to collagen through the action of procollagen N-proteinase and procollagen C-proteinase
• Lysyl oxidase catalyzes the formation of covalent cross-links between collagen molecules
• Defects in collagen synthesis or modification can lead to genetic disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome

Elastin

• Elastin is a connective tissue protein responsible for elasticity in lung, large arterial blood vessels, and some elastic ligaments
• Elastin is synthesized as a soluble monomer, tropoelastin, which is cross-linked by lysyl oxidase to form a fibrous mesh
• Elastin has a random coil conformation, allowing it to stretch and recoil
• Defects in elastin or fibrillin can lead to diseases such as Williams-Beuren syndrome and Marfan syndrome

Fibronectin

• Fibronectin is a glycoprotein found in ECM, plasma, and on cell surfaces
• Fibronectin interacts with collagen, proteoglycans, and integrins to regulate cell adhesion and migration
• Fibronectin contains an RGD sequence that binds to integrins, mediating cell-ECM interactions

Glycosaminoglycans (GAGs)

• GAGs are unbranched polysaccharides composed of repeating disaccharides
• GAGs include hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, and heparan sulfate
• GAGs are anionic, highly hydrated, and contribute to tissue turgor and sieving properties
• GAGs are covalently linked to core proteins to form proteoglycans, which are crucial for ECM structure and function

Proteoglycans

• Proteoglycans are proteins with covalently linked GAGs
• Proteoglycans are found in all tissues, primarily in ECM, and are involved in cell signaling and behavior
• Proteoglycans can bind growth factors, modulating their effects on cells
• Defects in proteoglycan synthesis or degradation can lead to diseases such as mucopolysaccharidoses

Matrix Metalloproteinases (MMPs)

• MMPs are zinc-containing proteases that cleave ECM proteins
• MMPs are regulated by transcriptional control, proteolytic activation, and inhibition by TIMPs (tissue inhibitors of metalloproteinases)
• Coordinated expression of MMPs and TIMPs is essential for tissue growth and remodeling
• Dysregulation of MMPs has been implicated in various diseases, including cancer and atherosclerosis

Extracellular Matrix (ECM)

• ECM is a complex network of proteins and carbohydrates that provides structural support, maintains tissue architecture, and regulates various cellular functions
• Composition of ECM varies in different tissues, depending on their functions
• ECM protects organs, provides elasticity, and keeps cells, large molecules, and microorganisms in place
• ECM also provides a porous pathway for the diffusion of nutrients and oxygen to individual cells

Collagen

• Collagen is the most abundant fibrous protein in the human body (~25% of all proteins)
• Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
• Collagen is composed of three α-chains, each approximately 1000 amino acids long, with a repeating pattern of Gly-X-Y
• Hydroxyproline and hydroxylysine are essential for collagen stability and cross-linking
• Collagen triple helix is a rod-like molecule, 300 nm long and 1.5 nm thick, with a molecular weight of 300 kDa
• Collagen has high tensile strength due to its unique structure and cross-linking

Collagen Synthesis and Modification

• Collagen synthesis occurs intracellularly, with post-translational modifications such as hydroxylation and glycosylation
• Procollagen is converted to collagen through the action of procollagen N-proteinase and procollagen C-proteinase
• Lysyl oxidase catalyzes the formation of covalent cross-links between collagen molecules
• Defects in collagen synthesis or modification can lead to genetic disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome

Elastin

• Elastin is a connective tissue protein responsible for elasticity in lung, large arterial blood vessels, and some elastic ligaments
• Elastin is synthesized as a soluble monomer, tropoelastin, which is cross-linked by lysyl oxidase to form a fibrous mesh
• Elastin has a random coil conformation, allowing it to stretch and recoil
• Defects in elastin or fibrillin can lead to diseases such as Williams-Beuren syndrome and Marfan syndrome

Fibronectin

• Fibronectin is a glycoprotein found in ECM, plasma, and on cell surfaces
• Fibronectin interacts with collagen, proteoglycans, and integrins to regulate cell adhesion and migration
• Fibronectin contains an RGD sequence that binds to integrins, mediating cell-ECM interactions

Glycosaminoglycans (GAGs)

• GAGs are unbranched polysaccharides composed of repeating disaccharides
• GAGs include hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, and heparan sulfate
• GAGs are anionic, highly hydrated, and contribute to tissue turgor and sieving properties
• GAGs are covalently linked to core proteins to form proteoglycans, which are crucial for ECM structure and function

Proteoglycans

• Proteoglycans are proteins with covalently linked GAGs
• Proteoglycans are found in all tissues, primarily in ECM, and are involved in cell signaling and behavior
• Proteoglycans can bind growth factors, modulating their effects on cells
• Defects in proteoglycan synthesis or degradation can lead to diseases such as mucopolysaccharidoses

Matrix Metalloproteinases (MMPs)

• MMPs are zinc-containing proteases that cleave ECM proteins
• MMPs are regulated by transcriptional control, proteolytic activation, and inhibition by TIMPs (tissue inhibitors of metalloproteinases)
• Coordinated expression of MMPs and TIMPs is essential for tissue growth and remodeling
• Dysregulation of MMPs has been implicated in various diseases, including cancer and atherosclerosis

Extracellular Matrix (ECM)

• ECM is a complex network of proteins and carbohydrates that provides structural support, maintains tissue architecture, and regulates various cellular functions
• Composition of ECM varies in different tissues, depending on their functions
• ECM protects organs, provides elasticity, and keeps cells, large molecules, and microorganisms in place
• ECM also provides a porous pathway for the diffusion of nutrients and oxygen to individual cells

Collagen

• Collagen is the most abundant fibrous protein in the human body (~25% of all proteins)
• Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
• Collagen is composed of three α-chains, each approximately 1000 amino acids long, with a repeating pattern of Gly-X-Y
• Hydroxyproline and hydroxylysine are essential for collagen stability and cross-linking
• Collagen triple helix is a rod-like molecule, 300 nm long and 1.5 nm thick, with a molecular weight of 300 kDa
• Collagen has high tensile strength due to its unique structure and cross-linking

Collagen Synthesis and Modification

• Collagen synthesis occurs intracellularly, with post-translational modifications such as hydroxylation and glycosylation
• Procollagen is converted to collagen through the action of procollagen N-proteinase and procollagen C-proteinase
• Lysyl oxidase catalyzes the formation of covalent cross-links between collagen molecules
• Defects in collagen synthesis or modification can lead to genetic disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome

Elastin

• Elastin is a connective tissue protein responsible for elasticity in lung, large arterial blood vessels, and some elastic ligaments
• Elastin is synthesized as a soluble monomer, tropoelastin, which is cross-linked by lysyl oxidase to form a fibrous mesh
• Elastin has a random coil conformation, allowing it to stretch and recoil
• Defects in elastin or fibrillin can lead to diseases such as Williams-Beuren syndrome and Marfan syndrome

Fibronectin

• Fibronectin is a glycoprotein found in ECM, plasma, and on cell surfaces
• Fibronectin interacts with collagen, proteoglycans, and integrins to regulate cell adhesion and migration
• Fibronectin contains an RGD sequence that binds to integrins, mediating cell-ECM interactions

Glycosaminoglycans (GAGs)

• GAGs are unbranched polysaccharides composed of repeating disaccharides
• GAGs include hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, and heparan sulfate
• GAGs are anionic, highly hydrated, and contribute to tissue turgor and sieving properties
• GAGs are covalently linked to core proteins to form proteoglycans, which are crucial for ECM structure and function

Proteoglycans

• Proteoglycans are proteins with covalently linked GAGs
• Proteoglycans are found in all tissues, primarily in ECM, and are involved in cell signaling and behavior
• Proteoglycans can bind growth factors, modulating their effects on cells
• Defects in proteoglycan synthesis or degradation can lead to diseases such as mucopolysaccharidoses

Matrix Metalloproteinases (MMPs)

• MMPs are zinc-containing proteases that cleave ECM proteins
• MMPs are regulated by transcriptional control, proteolytic activation, and inhibition by TIMPs (tissue inhibitors of metalloproteinases)
• Coordinated expression of MMPs and TIMPs is essential for tissue growth and remodeling
• Dysregulation of MMPs has been implicated in various diseases, including cancer and atherosclerosis

Extracellular Matrix (ECM)

• ECM is a complex network of proteins and carbohydrates that provides structural support, maintains tissue architecture, and regulates various cellular functions
• Composition of ECM varies in different tissues, depending on their functions
• ECM protects organs, provides elasticity, and keeps cells, large molecules, and microorganisms in place
• ECM also provides a porous pathway for the diffusion of nutrients and oxygen to individual cells

Collagen

• Collagen is the most abundant fibrous protein in the human body (~25% of all proteins)
• Found in skin, cartilage, bones, teeth, tendons, ligaments, and cornea
• Collagen is composed of three α-chains, each approximately 1000 amino acids long, with a repeating pattern of Gly-X-Y
• Hydroxyproline and hydroxylysine are essential for collagen stability and cross-linking
• Collagen triple helix is a rod-like molecule, 300 nm long and 1.5 nm thick, with a molecular weight of 300 kDa
• Collagen has high tensile strength due to its unique structure and cross-linking

Collagen Synthesis and Modification

• Collagen synthesis occurs intracellularly, with post-translational modifications such as hydroxylation and glycosylation
• Procollagen is converted to collagen through the action of procollagen N-proteinase and procollagen C-proteinase
• Lysyl oxidase catalyzes the formation of covalent cross-links between collagen molecules
• Defects in collagen synthesis or modification can lead to genetic disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome

Elastin

• Elastin is a connective tissue protein responsible for elasticity in lung, large arterial blood vessels, and some elastic ligaments
• Elastin is synthesized as a soluble monomer, tropoelastin, which is cross-linked by lysyl oxidase to form a fibrous mesh
• Elastin has a random coil conformation, allowing it to stretch and recoil
• Defects in elastin or fibrillin can lead to diseases such as Williams-Beuren syndrome and Marfan syndrome

Fibronectin

• Fibronectin is a glycoprotein found in ECM, plasma, and on cell surfaces
• Fibronectin interacts with collagen, proteoglycans, and integrins to regulate cell adhesion and migration
• Fibronectin contains an RGD sequence that binds to integrins, mediating cell-ECM interactions

Glycosaminoglycans (GAGs)

• GAGs are unbranched polysaccharides composed of repeating disaccharides
• GAGs include hyaluronic acid, chondroitin sulfate, keratan sulfate, heparin, and heparan sulfate
• GAGs are anionic, highly hydrated, and contribute to tissue turgor and sieving properties
• GAGs are covalently linked to core proteins to form proteoglycans, which are crucial for ECM structure and function

Proteoglycans

• Proteoglycans are proteins with covalently linked GAGs
• Proteoglycans are found in all tissues, primarily in ECM, and are involved in cell signaling and behavior
• Proteoglycans can bind growth factors, modulating their effects on cells
• Defects in proteoglycan synthesis or degradation can lead to diseases such as mucopolysaccharidoses

Matrix Metalloproteinases (MMPs)

• MMPs are zinc-containing proteases that cleave ECM proteins
• MMPs are regulated by transcriptional control, proteolytic activation, and inhibition by TIMPs (tissue inhibitors of metalloproteinases)
• Coordinated expression of MMPs and TIMPs is essential for tissue growth and remodeling
• Dysregulation of MMPs has been implicated in various diseases, including cancer and atherosclerosis

This quiz covers the composition and functions of the extracellular matrix (ECM) in connective tissue, including its proteoglycans, fibrous proteins, and adhesion proteins. Learn how the ECM varies in different tissues and its role in protecting organs and providing elasticity.