Cell Biology - lecture 4 - Cell Adhesion

Learning Outcomes

  • By the end of the lecture, students should be able to:

    • Explain cell-cell adhesion mechanisms

    • Explain cell-matrix adhesion mechanisms

    • Describe the composition of the extracellular matrix (ECM)

Extracellular Matrix (ECM)

Overview

  • ECM is crucial for providing structural support and facilitating cellular functions.

Types of ECM

  1. Basement Membrane/Basal Lamina

    • A 2D sheet underlying epithelia, essential for cellular support and surrounds some non-epithelial cells.

      • Main components:

        • Collagen IV

        • Laminin

        • Nidogen

        • Perlecan

    • Epithelium

      • Cells are tightly packed, binding to each other.

  2. Fibrillar Matrix

    • A 3D matrix composed of various fibers where cells are buried in mesenchyme.

      • Main components:

        • Collagen I

        • Fibronectin

        • Elastin

        • Proteoglycans

      • Maintains integrity of the tissue’s organisation

    • Mesenchyme

      • Cells are sparse and embedded within the ECM.

Types of Junctional Complexes

Main Types

  1. Tight Junction: (occluding) junctional complex that seals off the neighbouring cells

  2. Adherens Junction: (anchoring) hold neighbouring cells together and holds the cells to the matrix

  3. Desmosome

  4. Gap Junction: couple cells via permeable pores and allows the passage of small, water-soluble molecules and ions

  5. Focal Adhesion

  6. Hemidesmosome

Desmosomes

  • pairs of dark, disk/button - like structures at cell-cell contact point

  • Function: Provide mechanical stability through connections to intermediate filaments.

Hemidesmosomes

  • half desmosomes that play a critical role in attaching epithelial cells to the ECM.

  • Linked to intermediate filaments for structural support.

Mechanical Support Against Stress

  • (hemi) desmosomes transduce intermediate filament stability to the outside of the cell

  • made of cadherin-family adhesion proteins

  • Examples of conditions associated with disruptions in intermediate filaments or desmosomal factors:

    • Epidermolysis Bullosa: Genetic mutations affect skin integrity.

    • Pemphigus: Autoantibodies target desmosomes, leading to blistering.

Specific Junction Types

Tight Junctions: claudin and occludin

  • Form barriers around the apical surface of epithelial cells.

  • Function: Prevent leakage and control substance passage.

Adherens Junctions

  • Linked to the actin cytoskeleton and contribute to tissue shape and stability.

  • Can mediate contractile forces that influence epithelial bending.

  • Uses cadherin proteins like E-cadherin

Focal Adhesions

  • Connect the actin cytoskeleton to the ECM via integrins.

  • Play a significant role in cell movement and migration.

  • Forms and detaches during cell movement

Cell Adhesion Molecules (CAMs)

Cadherins

  • Calcium-dependent adhesion molecules that require >1 mM Ca2+ for functionality.

  • Types of Cadherins:

    • E-cadherin: Found in many epithelial tissues.

    • N-cadherin: Present in neurons, heart, muscles.

    • P-cadherin: Located in placenta and skin.

    • VE-cadherin: Present in endothelial cells.

Cancer Metastasis and Cell Adhesion

  • Cancer metastasis is closely related to alterations in cell adhesion mechanisms.

Conclusion

  • The interplay of different adhesion mechanisms and structures is vital for cell integrity and function.

  • Understanding these interactions aids in the comprehension of developmental biology, diseases, and therapeutic strategies.