Cell Biology: Extracellular Interactions

Extracellular Interactions

• Cells in multicellular organisms are organized into tissues
• Cells interact with each other and extracellular materials
• These interactions regulate cell migration, growth, differentiation, and 3D tissue organization

Tissues

• Epithelium: A thin layer of tightly packed cells that cover surfaces and line cavities
  • Examples: epidermis (outer layer of skin)
• Endothelium: Specialized epithelium found inside blood vessels and lymphatic vessels
  • Single cell layer, controls bloodflow, regulates blood pressure, facilitates nutrient and waste exchange

Cell-Cell/Cell-ECM Interactions

• Apical Surface:
  • Tight Junctions: Seal gap between cells
  • Adherens junctions: Connect actin filaments between cells
  • Desmosome: Connects intermediate filaments between cells
  • Gap Junction: Passage of small water-soluble molecules
  • Hemidesmosome: Anchors intermediate filaments to extracellular matrix
• Basal Surface:
  • Focal adhesions: Anchors many cell types to ECM

Extracellular Components

• Glycocalyx: Cell coat of glycoproteins and glycolipids that project outward from the plasma membrane
  • Located at epithelial and endothelial cells
  • Mediates cell-cell and cell-substratum interactions
  • Provides mechanical protection
• Extracellular Matrix (ECM): Organized network of extracellular material
  • Provides physical and biochemical signals
  • Basement Membrane is part of the ECM, located beneath epithelial tissue and surrounds blood vessels, nerve fibers, muscles, and fat cells
  • Separates adjacent tissues, provides mechanical support, generates signals for cell survival, serves as substratum for cell migration, and acts as a barrier to macromolecules

Basement Membrane in Disease

• Glomerular basement membrane (GBM) filters blood in the kidney
  • Abnormal GBM impairs kidney filtration
  • Examples:
    • Diabetes: GBM thickens
    • Basement membrane disease: GBM becomes thin
    • GoodPasture’s syndrome: GBM is disrupted and thin

Basement Membrane Roles

• For Epithelium:
  • Anchorage: Anchors epithelial cells to connective tissue
  • Filtration: Controls substance exchange between epithelium and adjacent tissues
  • Compartmentalization: Separates epithelium from connective tissue
  • Cell differentiation and regeneration: Guides epithelial cell differentiation and repair
• For Endothelium:
  • Structural support: Provides a foundation for endothelial cells
  • Selective barrier: Regulates molecule passage between blood and tissues
  • Cell migration and repair: Aids endothelial cell migration and proliferation during angiogenesis and wound healing
  • Maintains separation: Prevents mixing of endothelial cells with underlying tissues

Extracellular Matrix Proteins

• Collagen: Main structural protein in ECM, most abundant protein in the human body, has high tensile strength
  • Types:
    • Fibrillar: Assemble into rigid, cable-like fibrils that package into thicker fibers. Found in skin, tendons, vasculature, cornea, bone, and organs
    • Non-Fibrillar: Non-helical lattice arrangement with globular domains found in basement membranes.
• Fibronectin: Glycoprotein secreted by fibroblasts, initially soluble, cells use it to build insoluble matrix
  • Plays a major role in cell adhesion, growth, migration, differentiation, wound healing, and embryonic development
• Laminin: Family of extracellular glycoproteins, organized into a cross-shaped molecule
  • Binds to cell-surface receptors, other laminin molecules, proteoglycans, and collagen of the basement membrane
  • Important for cell migration, growth, and differentiation

Collagen - Structure

• α chains of collagen: Contain hydroxylated proline residues
  • Contribute to stability of the triple helix structure
  • Vitamin C adds hydroxyl groups to lysine and proline, crucial for collagen structure
• Vitamin C deficiency: Leads to scurvy (poor wound healing, hair changes, skin bleeding)

Collagen - Types and Genetic Mutations

• Type I: Most abundant, found in tendons, skin, vessel walls, fibrocartilage, bones, and teeth
  • Mutations: Osteogenesis Imperfecta (brittle bone disease)
• Type II: Makes up 50% of cartilage protein
  • Mutations: Dwarfism
• Type III: Found in wound healing, vessel walls, skin, intestines, and the uterus
  • Mutations: Ehlers-Danlos Syndrome (type 4)

Fibronectin - Structure

• Binds to integrins (membrane-spanning receptor proteins) via Arg-Gly-Asp sequence
• Also binds to ECM via collagen, fibrin, and proteoglycans
• Protein dimer: Composed of 2 nearly identical monomers linked by disulfide bonds, containing distinct modules

Laminin - Functions

• Plays a pivotal role in the migration of primordial germ cells (PGCs)
  • PGCs arise in the yolk sac and travel to the developing gonad via regions rich in laminin.