Unit 08 Pt3

Unit 08: Junctions - In-depth Notes

Overview of the Extracellular Matrix (ECM)
  • Definition: The ECM is a macromolecular network produced by cells that provides structural and biochemical support to surrounding cells.
  • Components of ECM:
    • Various classes of molecules specific to different tissues.
    • Commonly found in connective tissues, produced primarily by fibroblasts (CT), chondroblasts (cartilage), and osteoblasts (bone).
    • Plays crucial roles in support, regulation, survival, development, migration, proliferation, shape, and function of tissues.
  • Basal Lamina: A specialized ECM in epithelial tissues crucial for allowing cell functions and interactions.
Composition of ECM
  • Proteoglycans: Composed of glycosaminoglycan (GAG) chains linked to core proteins.
    • Function: Forms hydrated gels, provides resistance to compression, facilitates diffusion in tissues.
  • Collagens: Major protein in ECM, making up about 25% of total protein mass.
    • Function: Provides tensile strength and structural integrity to tissues.
  • Elastin: Contributes to the elasticity of tissues like skin and blood vessels.
  • Fibronectin: A multidomain glycoprotein that assists in organizing the ECM and binds to integrins, facilitating cell-ECM interactions.
Glycosaminoglycans (GAGs)
  • Structure: Long unbranched polysaccharide chains made of repeating disaccharides, usually sulfated.
    • Types:
    • Hyaluronan
    • Chondroitin sulfate
    • Dermatan sulfate
    • Heparan sulfate
    • Keratan sulfate
  • Role in ECM: Occupy large volumes, form hydrated gels, attract cations and water, contributing to turgor and compressive strength.
Linking GAGs to Core Proteins
  • Hyaluronan: Simplest GAG, abundant in developing tissues and wound healing. Not sulfated and not typically linked to core proteins.
  • Other GAGs: Synthesized in the cell, linked to core proteins in the ER and Golgi, can be extensively modified (sulfation).
Proteoglycan Diversity
  • Core Proteins: Can vary widely; examples include aggrecan (with over 100 GAGs) and decorin (with 1 GAG).
    • Proteoglycans can form larger aggregates (e.g., aggrecan with hyaluronan).
Collagen Structure and Function
  • Types of Collagen:
    • Type I: Most abundant; found in skin and bone, forms fibrils and cable-like bundles.
    • Type IV: Network-forming; major component of basal lamina.
    • Types IX and XII: Fibril-associated collagens that help organize the fibrils.
  • Collagen Assembly: Helix stabilizes through hydrogen bonding, pro-peptides prevent premature fibril formation; self-assembly occurs near the cell surface.
Diseases Related to Collagen Defects
  • Scurvy: Caused by vitamin C deficiency affecting collagen synthesis, leading to fragile blood vessels and slow healing.
  • Osteogenesis Imperfecta: Genetic disorder caused by defective collagen, leading to brittle bones.
  • Ehlers-Danlos Syndrome: Results in fragile skin and joints due to collagen abnormalities.
Elastic Fibers in ECM
  • Function: Provide elasticity and allow tissues to recoil after being stretched.
    • Composed of elastin and microfibrils (e.g., fibrillin), necessary for structural integrity.
  • Elastin Characteristics: Highly hydrophobic, rich in proline and glycine, reversibly stretches and recoils due to its molecular structure.
Fibronectin and Its Role
  • Soluble vs. Insoluble form: Fibronectin can exist in soluble form in body fluids or as part of insoluble fibrils in the ECM.
  • Interaction with Cells: Fibronectin binds to integrins on cell surfaces, linking the ECM to the cytoskeleton, which helps transmit mechanical signals and organize extracellular structures.