1. The Extracellular Matrix Michael Malahy

2. ECM in Epithelial Sheets • 3 types of molecules abundant in ECM • Proteoglycans • Cushion cells and bind extracellular molecules • Collagen • Mechanical strength and resilience • Multiadhesive Matrix Proteins • Bind and cross-link adhesion receptors and other ECM components

3. Basal Lamina • Type IV Collagen • Trimeric, rod-like and globular, 2D • Laminins • Multiadhesive proteins that form 2D network with collagen and bind integrins • Entactin • Rod-like, cross-link collagen and laminin and helps incorporate other ECM components • Perlecan • Multidomain proteoglycan, binds and cross-links ECM components and cell-surface molecules

6. Type IV Collagen • Trimeric • Collagen α chains • Homo- or heterotrimeric • 1 or more 3-stranded segments • Each strand is left-handed • 3 strands twisted right-handed • Glycine, Proline and Hydroxyproline • Unusual abundance • Gly-X-Y • Lysine and Hydroxylysine

7. Figure 6.14

8. Figure 6.16

9. Proteoglycans • Membrane associated or secreted core proteins covalently linked to GAG chains • Glycosaminoglycans (GAG) • Sulfated Disaccharides • Syndecans • Cell-surface • Bind collagen, fibronectin and external signaling molecules such as growth factors • Regulate cellular metabolism and function

10. Fibrillar Collagens • Produced largely by Fibroblasts • Trimeric Type I Collagen Polymers • Fibrils • Larger bundles • Fibers • Form tendons • Gram for gram higher tensile strength than steel

11. Fibronectin • Multiadhesive matrix protein • All isoforms from alternative splicing of RNA from a single gene • Essential for migration differentiation in embryogenesis • Promote blood clotting and facilitate migration of immune cells to a wound • Attach cells to ECM by binding fibrous collagen and heparan sulfate proteoglycans to cell-surface adhesion receptors such as integrins

12. Fibronectins cont’d • Influence shape and movement of cells • Influence organization of the cytoskeleton • Dimer of 2 similar polypeptides • 6 functional regions with ligand-binding specificities • Each region contains certain repeating sequences • Type I, II or III • Beads on a string • Arg-Gly-Asp • RGD sequence recognizes several integrins