The Extracellular Matrix

Michael Malahy

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

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

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

Figure 6.14

Figure 6.16

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

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

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

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