Extracellular Matrix Review

Extracellular Matrix

Chapter Overview

  • Covering pages 103-114.

Objectives

  1. Understand the function and composition of the extracellular matrix (ECM).
  2. Learn about the formation and types of collagen fibers.
  3. Examine the components of ground substance with examples.
  4. Understand adhesive proteins and integrins, including their structure and function.
  5. Describe the composition and function of the basal lamina.

Extracellular Matrix (ECM)

  • Definition and Components:
    • ECM is a complex network of proteins and their polysaccharide components.
    • Key components include:
    • Structural proteins (collagens, elastins) that provide strength and flexibility.
    • Proteoglycans: Protein-polysaccharide complexes that form the matrix.
    • Adhesive glycoproteins: Fibronectins, laminins, and integrins that help cells attach to the matrix.

Functions of the Extracellular Matrix

  • The ECM serves several essential functions, including:
    • A. Reservoir function: Holds water, ions, nutrients, hormones, and signaling molecules.
    • B. Tissue strength and rigidity: Maintains the structural integrity of the tissue.
    • C. Maintains shape of tissues: Provides a framework to keep tissues structured.
    • D. Medium for metabolic exchange: Facilitates nutrient and waste exchange within tissues.

Components of the ECM

  1. Structural proteins (collagens and elastins):
    • Provide tensile strength and elasticity.
  2. Proteoglycans:
    • Formed from core proteins with attached glycosaminoglycans (GAGs).
    • Important types of GAGs include:
      • Dermatan sulfate
      • Chondroitin sulfate
      • Keratan sulfate
      • Heparan sulfate
  3. Adhesive glycoproteins:
    • Include fibronectins and laminins that anchor cells to the ECM.

Ground Substance

  • Definition: A highly hydrated, transparent mixture of macromolecules including:
    • Glycosaminoglycans (GAGs):
    • Linear polysaccharides composed of repeating disaccharide units:
      • Uronic acids (e.g., glucuronic or iduronic acid).
      • Hexosamines (e.g., glucosamine or galactosamine).
    • GAGs are usually covalently linked to a core protein in proteoglycans.
    • An exception is hyaluronic acid, which is not linked to anything.
    • Presence of sulfate and carboxyl groups enhances hydrophilicity and gives a negative charge.
Examples of Common GAGs
  • Chondroitin sulfate
  • Keratan sulfate
  • Hyaluronate

Proteoglycans

  • Composition:
    • Made of core protein with various attached GAGs, including:
    • Dermatan sulfate
    • Chondroitin sulfate
    • Keratan sulfate
    • Heparan sulfate

Collagen Fibers in the ECM

  • Collagen Overview:
    • A family of 25+ proteins characterized by high tensile strength.
    • Synthesized initially as procollagen, which then forms tropocollagen upon cleavage, aggregating into fibrils and fibers.
  • Collagen Synthesis Process:
    1. Formation of mRNA for collagen chain in the nucleus.
    2. Synthesis of precursor chains of preprocollagen in the rough endoplasmic reticulum (RER).
    3. Hydroxylation of certain residues in a vitamin C-dependent manner.
    4. Assembly of procollagen into a triple helix, then transported via secretory vesicles.
    5. Extracellularly, procollagen peptidases cleave non-helical ends, allowing fibrillogenesis.
  • Types of Collagen:
    • Type I: Ubiquitous; large fibers found in skin, bone, tendon, cartilage.
    • Type II: Found in hyaline and elastic cartilage; contains only fibrils.
    • Type III: Reticular collagen found in loose connective tissues.
    • Type IV: Mesh-like structure; present in the basal lamina.

Types of Collagens and Their Characteristics

  • Table of Collagens:
    • Type I: Long fibrils, present in skin, bone, tendon.
    • Type II: Fibril-associated, found in cartilage.
    • Type III: Forms loose networks, found in lymphatic system.
    • Type IV: Forms sheets in the basal lamina.
    • Others include frail collagen types involved in specialized tissues.

Adhesive Glycoproteins

  1. Fibronectin:
    • Binds cells to ECM components such as collagen and heparan sulfate.
    • Structure includes folded rod-like domains with various binding sites.
    • Plays a crucial role in guiding cell migration and adhesion.
  2. Laminin:
    • Found in the basal lamina and binds epithelial cells to ECM.
    • Provides specific binding sites for collagen and integrins.

Integrins

  • Definition: A large family of cell surface receptors that connect cells to fibronectins, laminins, and collagen in the ECM.
  • Functions:
    • Integrate cytoskeleton with ECM.
    • Regulate cell movement and attachment, playing critical roles in cell signaling and migration.

Basal Lamina

  • Definition: A thin sheet of specialized ECM that supports and separates epithelial cells from connective tissues.
  • Composition:
    • Type IV collagen, laminins, entactin, and perlecan.
  • Functions:
    • Provides structural support and acts as a permeability barrier for epithelial cells.