Chapter 20 - Integrating Cells into Tissues

20.1 Cell-Cell and Cell–Extracellular Matrix Adhesion: An Overview

• Slide 1: Cell-cell and cell–extracellular matrix (ECM) interactions are critical for:- Assembling cells into tissues.

  • Controlling cell shape and function.

  • Determining the developmental fate of cells and tissues.

• Slide 2: Cell-adhesion molecules (CAMs) mediate direct cell-cell adhesions, including:- Homotypic adhesions: adhesion between same type of cell.

  • Heterotypic adhesions: adhesion between different types of cells.

• Slide 3: Adhesion receptors mediate cell-matrix adhesions.

Overview of Major Cell-Cell and Cell-Matrix Adhesive Interactions

• Slide 4: Cell-Cell Adhesions- Tight Junctions - Located on the apical surface

  • Adherens Junctions

  • Desmosomes

  • Gap Junctions - Contain Connexons

• Slide 5: Cell-Matrix Adhesions- Focal Contacts - Located on the basal surface

  • Hemidesmosomes

• Slide 6: Cell-adhesion molecules (CAMs)

• Slide 7: Adhesion receptors

• Slide 8: Extracellular matrix (ECM)- Basal lamina

  • Connective tissue

Major Families of Cell-Adhesion Molecules (CAMs) and Adhesion Receptors

• Slide 9: Homophilic Interactions:- Cadherins (E-cadherin):- Contain calcium-binding sites.

• Slide 10: Ig-Superfamily CAMs (NCAM)- Contain Ig domain.

• Slide 11: Heterophilic Interactions:- Integrins (\alphav\beta3):- Contain Type III fibronectin repeat.

• Slide 12: Selectins (P-selectin):- Contain Lectin domain, bind to sugars.

Model for the Generation of Cell-Cell Adhesions

• Slide 13: Cis (Lateral) Interactions: CAMs interact with each other on the same cell surface.

• Slide 14: Trans Interactions: CAMs interact with CAMs on adjacent cell surfaces.

• Slide 15: Cis + Trans Interactions: Combination of lateral and transverse interactions to strengthen adhesion.

Extracellular Matrix (ECM) Components

• Slide 16: Extracellular Matrix Proteins- Collagens- Fibrillar collagens (e.g., types I, II, and III)
  - Sheet forming (e.g., type IV)

• Slide 17: Multi-adhesive matrix proteins- Laminin
  - Fibronectin
  - Nidogen/entactin

• Slide 18: Proteoglycans- Perlecan

Variation in the Relative Density of Cells and ECM in Different Tissues

• Slide 19: (a) Connective Tissue:- Features fibroblasts surrounded by ECM.

• Slide 20: (b) Tightly Packed Epithelial Cells:- Shows adjacent cell membranes and nuclei with minimal ECM.

Functions of the Extracellular Matrix (ECM)

• Slide 21: 1. Anchoring and engulfing cells to maintain solid tissue architecture and define tissue boundaries.

• Slide 22: 2. Determining the biomechanical properties (stiffness/elasticity, porosity, shape) of the extracellular environment.

• Slide 23: 3. Controlling cellular polarity, survival, proliferation, differentiation, and fate.

• Slide 24: 4. Inhibiting or facilitating cell migration.

• Slide 25: 5. Binding to and acting as a reservoir of growth factors; the ECM may:- Help generate an extracellular concentration gradient of the growth factor.

  • Serve as a co-receptor for the growth factor.

  • Aid in proper binding of the growth factor to its receptor.

Disruptions in Cell-Matrix and Cell-Cell Interactions

• Slide 26: Antibodies to fibronectin block branching morphogenesis in developing mouse tissues.

• Slide 27: Interfere with tissue development.

Inactivating the Genes for Some ECM Proteins

• Slide 28: Results in defective skeletal development in mice.- Wild type.

  • Collagen II deficiency.

  • Perlecan deficiency.

Integrin Adhesion Receptor-Mediated Signaling Pathways Control Diverse Cell Functions

• Slide 29: ECM Ligand binds to Integrin (adhesion receptor).

• Slide 30: Activation of receptor tyrosine kinase.

• Slide 31: Activation of various adapters and signaling kinases.

• Slide 32: Activation of PI3K, GRB2, Rac/Rho/Cdc42 (small GTPases).

• Slide 33: Classic signaling pathways: Akt/PKB, Ras.

• Slide 34: Leads to cellular responses to adhesion receptor signaling:- Cell proliferation (cycle).

  • Cell survival.

  • Cytoskeletal organization.

  • Cell migration.

  • Gene transcription.

Models of Domains in Mechanosensor Proteins Responding to Mechanical Forces

• Slide 35: (a) Fibronectin type III domain- Mechanical force (stretching) can expose previously inaccessible binding sites.

• Slide 36: (b) Talin five-helix bundle domain- Mechanical force (stretching) can alter the conformation of the domain.

20.2 Cell-Cell and Cell–Extracellular Junctions and Their Adhesion Molecules

• Slide 37: Anchoring junctions include adherens junctions, focal contacts, desmosomes, and hemidesmosomes.

• Slide 38: Cadherins and integrins mediate cell-cell and cell-ECM junctions.

• Slide 39: Tight junctions define epithelial cell polarity and regulate extracellular flow.

• Slide 40: Gap junctions connect the cytoplasms of adjacent cells for metabolic and electrical coupling.

Principal Types of Epithelia

• Slide 41: (a) Simple columnar epithelia:- Elongated cells – including mucus-secreting cells and absorptive cells.

• Slide 42: (b) Simple squamous epithelia:- Thin cells – cells lining blood vessels and body cavities.

• Slide 43: (c) Transitional epithelia:- Several layers of cells with different shapes – line certain cavities subject to expansion.

• Slide 44: (d) Stratified squamous (nonkeratinized) epithelia:- Line surfaces such as the mouth and vagina.

Principal Types of Cell Junctions Connecting the Columnar Epithelial Cells Lining the Small Intestine

• Slide 45: Tight junction.

• Slide 46: Adherens junction.

• Slide 47: Desmosome.

• Slide 48: Gap junction.

• Slide 49: Hemidesmosome.

• Slide 50: Actin and myosin filaments.

• Slide 51: Intermediate filaments.

• Slide 52: Basal lamina.

• Slide 53: Connective tissue.

• Slide 54: Apical, Lateral, and Basal Surfaces.

• Slide 55: Microvillus.

Cell Junctions

• Slide 56: Anchoring junctions:

  1. Adherens junctions: Cell-cell; Cadherins; Actin; Catenins, vinculin; Shape, tension, signaling.

  2. Desmosomes: Cell-cell; Desmosomal cadherins; Intermediate filaments; Plakoglobin, plakophilins; Strength, durability.

  3. Hemidesmosomes: Cell-matrix; Integrin (\alpha6\beta4); Intermediate filaments; Plectin, dystonin; Shape, rigidity.

  4. Focal, fibrillar, and 3-D adhesions: Cell-matrix; Integrins; Actin; Talin, kindlin; Shape, signaling, force transmission, cell movement.

• Slide 57: Tight junctions: Cell-cell; Occludin, claudins; Actin; ZO-1,2,3; Controlling solute flow.

• Slide 58: Gap junctions: Cell-cell; Connexins; Via adapters; ZO-1,2,3; Communication, transport.

• Slide 59: Plasmodesmata: Cell-cell; Undefined; Actin; NET1A (plants only); Communication, transport.

E-cadherin Mediates Ca^{2+}-dependent Adhesion of L Cells

• Slide 60: No cadherin transgene.

• Slide 61: Cadherin transgene.

• Slide 62: With calcium.

• Slide 63: Without calcium.

Desmosomes

• Slide 64: Plasma membrane.

• Slide 65: Intercellular space.

• Slide 66: Intermediate filaments.

• Slide 67: Cytoplasmic plaques.

• Slide 68: Desmoglein and desmocollin.

Tight Junctions

• Slide 69: Seal off body cavities.

• Slide 70: Restrict diffusion of components between membranes.

• Slide 71: Honeycomb-like network in freeze-fracture preparation.

Transcellular and Paracellular Pathways of Transepithelial Transport

• Slide 72: Transcellular pathway.

• Slide 73: Paracellular pathway.

• Slide 74: Apical membrane.

• Slide 75: Basolateral membrane.

• Slide 76: Tight junction.

Gap Junctions

• Slide 77: Connexon hemichannel.

• Slide 78: Gap-junction channel.

• Slide 79: Cytosol.

• Slide 80: Intercellular gap.

• Slide 81: Membrane.

• Slide 82: Channel diameter ~14 Å.

• Slide 83: Outermost diameter ~90 Å.

• Slide 84: Intercellular Gap: 38 Å + 38 Å = 76 Å

• Slide 85: Membrane: 19 Å + 19 Å = 38 Å