chap 7

EXTRACELLULAR & INTRACELLULAR MATRICES

Learning Outcomes

  • Definition of ECM: Understand the Extracellular Matrix (ECM) and its significance in biological systems.

  • Main Functions of ECM:

    • Binds cells together and provides structural support.

    • Acts as a reservoir for hormones and morphogens.

    • Serves as an area for cell movement, particularly during development, differentiation, growth, and wound healing.

    • Examples of ECM include tendons, bones, and kidney glomeruli.

  • Degeneration of ECM: Recognize the consequences of ECM degeneration.

  • Assembly of ECM (Collagen): Understand the process by which ECM, particularly collagen, is formed and organized.

  • Structural Composition of ECM: Identify the various components of ECM and their specific functions.

  • Molecular Components of ECM: Name the molecular structures that comprise ECM.

  • Cell Linking to ECM: Explain how cells connect and interact with the ECM.

  • Unique Characteristics of ECM: Recognize the distinguishing features of ECM.

  • Cytoskeleton Types: Identify and categorize the different types of cytoskeleton available in cells.

  • Structural Composition of Cytoskeleton: Describe the individual structural components of cytoskeletons, such as actin filaments, intermediate filaments, and microtubules.

  • Structure and Function Relationship: Relate the structural properties of cytoskeleton components to their functional roles in cellular dynamics.

General Organization of Tissues

  • Embryonic Layer & Cell Types:

    • Ectoderm: Forms the Central Nervous System (CNS), retina (neuroectoderm), pigment cells, neurons, glia, and melanocytes.

    • Epithelium: Includes skin, hair, mammary glands (keratinocytes).

    • Endoderm: Comprises gut, liver, pancreas, lung, and other glands.

    • Mesoderm: Forms the urogenital tract and muscle tissues (e.g., skeletal, cardiac, smooth muscle).

    • Connective Tissue: Components include interstitium and blood, featuring various cell types (e.g., myocytes, fibroblasts, leukocytes).

Overview & Functions of ECM

  • Definition of ECM:

    • ECM is a complex material secreted and deposited by cells, forming a network of proteins and carbohydrates.

  • Functions of ECM:

    • Binds and supports cells.

    • Serves as a reservoir for biological molecules.

    • Facilitates cellular movement during crucial biological processes.

Composition & Structural Diversity of ECM

  • Analogy of ECM:

    • Analogy of egg yolks (cells) and egg whites (ECM) illustrates the connectivity and communication role of ECM among cells.

  • ECM Degeneration: Degeneration is likened to an egg poaching, where loss of water content disrupts the functions and connections within ECM.

Types of ECM

  • Basement Membrane:

    • Found in epithelial, endothelial, muscle, fat, and nerve tissues.

  • Elastic Fibers:

    • Present in skin, lungs, and large blood vessels, known for their elasticity.

  • Stromal or Interstitial Matrix:

    • Found in bones, teeth, cartilage, tendons, and ligaments.

Cells & ECM Receptors

  • Key Receptors for ECM:

    • Integrins, dystroglycans, syndecans, and muscle-specific kinase (MuSK) are crucial for cell recognition and response to ECM.

Types of ECM Components

  • Collagens: Various types provide structural integrity.

  • Proteoglycans: Serve functions such as binding water and regulating growth factors.

  • Glycoproteins: Includes laminins, nidogens, fibronectins, and others that link cellular components.

  • Matricellular Proteins: Such as SPARC, thrombospondins, osteopontin, and tenascins.

Features of ECM Proteins

  • Modular Nature:

    • Most ECM proteins are large, glycosylated, and contain repetitive domains for versatile functions (e.g., fibronectin type III repeats).

Basement Membranes

  • Definition: Specialized layers of ECM near all epithelia and muscle cells; crucial in maintaining structural integrity.

Collagen Diversity & Structure

  • Types of Collagen:

    • Type I: Found in skin, tendons, bones, providing tensile strength.

    • Type II: Located in cartilage.

    • Type IV: Structural component of basement membranes.

  • Collagen Structure:

    • Composed of glycine, proline, and hydroxyproline subunits, typically forming a triple helix.

Collagen Biosynthesis

  • Synthesis Process:

    • Initiated in the Endoplasmic Reticulum (ER) where polypeptide chains form soluble procollagen. Post-translational modifications occur in the Golgi apparatus, followed by secretion and assembly into collagen fibers outside the cell.

Proteoglycans

  • Characteristics:

    • Composed of a core protein with carbohydrate chains, fostering hydration and space occupation in tissues.

  • Functions:

    • Include shock absorption, water retention, and interaction with collagen fibers.

Hyaluronan

  • Also known as hyaluronic acid; provides cell-free space promoting cell migration and proliferation.

Fibronectin and Laminin

  • Fibronectin:

    • A glycoprotein crucial for cell adhesion, migration, and organizing the ECM.

  • Laminin:

    • Vital for cellular adhesion, signaling, and providing a scaffold for tissue structure.

Cell-Matrix Adhesion

  • Integrins:

    • Essential membrane proteins bridging the ECM to the cytoskeleton, facilitating cell attachment.

  • Hemidesmosomes:

    • Key structures that anchor basal cells to the basal lamina using cytoskeletal attachments.

Collagen Diseases

  • Diseases Involving Collagen:

    • Fibrosis: Excess collagen leading to tissue stiffening.

    • Osteogenesis Imperfecta: Mutations in type I collagen leading to brittle bones.

    • Scurvy: Vitamin C deficiency impacting collagen stability and function.

ECM Degeneration Consequences

  • Results in various health issues, including arthritis, delayed tissue repair, and increased malnutrition risk, affecting overall physical stability and environmental sensitivity.

Classifications of Cytoskeleton & Protein Composition

  • Types of Filaments:

    • Actin filaments (microfilaments), Intermediate filaments, and Microtubules serve crucial roles in cell mechanics, shape, and intracellular transport.

Cytoskeleton Functions

  • Essential for establishing cell shape, providing mechanical strength, enabling locomotion, and facilitating intracellular transport.

Conclusion

  • Importance of ECM:

    • Acts as structural support, compartmentalizes tissue, presents signals for cell communication, and guides migration during development and healing.