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Lecture V and VI: Chapter 20 Integrating Cells into Tissues
20. Epithelia

20.1 Cell-Cell and Cell

–Extracellular Matrix Adhesion: An Overview

  • Cells adhere to each other and to the extracellular matrix (ECM).

20.2 Cell-Cell and Cell

–Extracellular Matrix Junctions and Their Adhesion Molecules

  • Cell Junction Types and Main Functions:

    • Tight Junction: Forms a barrier, preventing leakage between cells (paracellular transport control).

    • Adherens Junction: Provides strong adhesion and connects to actin filaments via cadherins.

    • Desmosome: Provides structural support and adhesion, linking to intermediate filaments via cadherins.

    • Gap Junction: Facilitates direct cell-to-cell communication via connexins.

    • Hemidesmosome: Anchors cells to the ECM through integrin molecules.

  • Key Adhesion Molecules (CAMs):

    • Cadherins (in adherens junctions and desmosomes)

    • Integrins (in hemidesmosomes, involved in cell-ECM adhesion and signaling)

    • Occludin and Claudins (in tight junctions, control paracellular permeability)

20.3 The Extracellular Matrix I: The Basal Lamina

  • Basal Lamina:

    • A thin, supportive layer found beneath epithelial tissues.

    • Composed primarily of type IV collagen and laminin.

    • Functions: Separates epithelia from connective tissues, provides structural support, and acts as a selective filter.

20.4 The Extracellular Matrix II: Connective Tissue

  • Connective Tissue Composition:

    • Consists mainly of ECM, synthesized by fibroblasts.

    • Main components: Collagens, Glycosaminoglycans (GAGs), Proteoglycans, Multi-adhesive proteins (e.g., fibronectin).

  • Functional Components of ECM: Provides strength, elasticity, and structural integrity.

Structures and Functions of Cell Junctions

  • Claudin/Occludin Proteins: Negatively charged proteins crucial for tight junction barrier function.

  • Tight Junction Functionality: Regulates paracellular transport of ions, water, and solutes between cells.

  • Transepithelial Transport Mechanisms:

    • Transcellular Pathway: Molecules pass directly through epithelial cells (crossing apical and basolateral membranes).

    • Paracellular Pathway: Molecules pass between cells, regulated/blocked by tight junctions.

The Extracellular Matrix

  • Composition of the ECM: Made of proteins and polysaccharides, varying by tissue. Secreted mainly by fibroblasts.

  • Key ECM Components:

    • Fibrous structural proteins (collagen and elastin).

    • Hydrated gels (hyaluronate).

    • Adhesion glycoproteins (fibronectin and laminin).

  • Functions of the Extracellular Matrix:

    1. Anchors cells, shaping tissue architecture.

    2. Determines biomechanical properties (e.g., tissue stiffness).

    3. Controls cell polarity, survival, development, and proliferation.

    4. Regulates cell migration.

    5. Serves as a reservoir for growth factors.

    6. Activates cell signaling receptors.

Basal Lamina and its Structure

  • Basal Lamina Structure: Mesh of type IV collagen and laminin networks, interlinked by nidogen and perlecan.

  • Laminin Protein Structure: Laminins are multi-domain proteins with various isoforms.

Collagens

  • Collagen Characteristics:

    • Most abundant protein in mammals.

    • Composed of repeating units rich in glycine, proline, and hydroxyproline, forming a stable triple helix.

    • Types: Fibrillar collagens (e.g., type I, II, III), sheet-forming (type IV in basal lamina), and transmembrane collagens.

  • Collagen Functions: Provides structural framework, tensile strength, and resilience against forces in tissues.

Proteoglycans

  • General Structure and Function: Core protein with covalently attached glycosaminoglycans (GAGs). Form hydrated gels that resist compression and fill space.

  • Aggrecan: Major proteoglycan in cartilage, crucial for resisting compression and lubricating joint spaces.

Glycosaminoglycans (GAGs)

  • Classes of GAGs: Hyaluronan, heparan sulfate, keratan sulfate, chondroitin sulfate. They are unbranched polysaccharide chains, highly negatively charged.

Elastin in Connective Tissue

  • Elastin's Role: Main component of elastic fibers, providing elasticity and ability to stretch and recoil in tissues (e.g., skin, blood vessels, lungs).

  • Diseases Associated with Elastin Defects: Marfan syndrome (due to fibrillin-1 mutations), affecting skeletal and cardiovascular systems.

Diapedesis and Tissue Remodeling

  • Diapedesis: Process where leukocytes exit the bloodstream into tissues, involving adhesion to endothelium via selectins and integrins.

  • Tissue Remodeling: Fibroblasts produce ECM and respond to signaling molecules to regulate the microenvironment, critical during wound healing and inflammation.

Summary

  • Key Points for Biomedical Science:

    1. Understanding cell adhesion molecules (Cadherins, Integrins, Occludins/Claudins) and junction types (Tight, Adherens, Desmosomes, Gap, Hemidesmosomes) is fundamental to tissue organization and function.

    2. The Extracellular Matrix (ECM) provides structural integrity, influences cell behavior (polarity, survival, migration, proliferation), and acts as a signaling hub.

    3. Key ECM components include collagens (strength), proteoglycans/GAGs (hydration, compression resistance), and elastin (elasticity). Defects in these components lead to various diseases.