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