Cell Bio ECM (7)

• Collagens
• Proteoglycans
• Matricellular Proteins (Adhesive Glycoproteins)
• Integrins
• Cadherins
• CAMs (Cell Adhesion Molecules)
• Elastic fibers (Elastin)
• Matrix Metalloproteases (MMPs)

• provide structural integrity for bone and cartilage; also major component of basement membranes
• •Type I: fibril-forming & found almost everywhere (bONE especially)
• •Type II: fibril-forming & almost exclusively in cartilage (car-two-lage)
• •Type IV: network/sheet-forming type that plays a role in basement membranes (basal lamina)
• •Type XVIII: basal lamina around blood vessels

• •Type II = cartilage collagen
• •Type IV = epithelial basement membrane/basal lamina collagens

• fragment of Type XVIII (18) Collagen that inhibits angiogenesis
• • likely anti-cancer by inducing apoptosis in endothelial cells

• 1. Goodpasture’s Syndrome
• 2. Alport Syndrome
• 3. Menke’s Disease
• 4. Ehler-Danlos Syndrome
• 5. Scurvy
• 6. Osteogenesis Imperfecta
• - G A M ED S OI -
• O(i)MG SE(d)A! OMG SEA!

• autoimmune disease in which antibodies to Type IV collagen destroy the basement membrane in the lungs and kidneys
• •this is the one where you have to consider which is worse, losing kidney or lung function?
• •treatment = corticosteroids, immunosuppressants

•genetic disorder in which type IV collagen is absent or non-functional --> KIDNEY failure

• X-linked recessive disease --> causes a deficiency in copper utilization --> results in faulty collagen cross-linking
• •causes developmental delays, seizures, failure to thrive, & characteristically kinky, colorless, & easily broken hair

• a connective tissue disorder --> results from a defect in collagen synthesis & assembly
• •without the collagen to stabilize the connective tissue, tissues become more elastic (bendy fingers)
• •has consequences in both the musculoskeletal & vascular system

Vitamin C deficiency prevents cross-linking of collagens; deficiency leads to spots on the skin, spongy gums, & bleeding from mucous membranes

• autosomal dominant disorder --> causes a mutation in Type I collagen
• •mutated collagen in bones results in brittle bones & multiple fractures (case study where girl was taken away from her parents)

• 1) Regulate hydration state of tissues, especially cartilage
• 2) Provide resistance to impact (shock absorbers) in cartilage
• 3) Act as reservoirs for growth factors and cytokines
• It’s the carbs that count!

• •can be caused by either 1) defective proteoglycans or 2) defective Collagen II
• •clinical correlate: collagen II OR chondroitin proteoglycans
• •flattened nose bridge and malformed legs, feet, toes, forearm & fingers

• •secreted and bound tightly to cell surface through interactions with integrins; help attach cells to each other and the ECM
• •they help regulate proliferation, motility, and differentiation because they're attached to cytoskeleton & signaling pathways

• 1) fibronectin
• 2) laminin
• 3) CCN proteins

type of matricellular protein found in connective tissue/mesenchymal matrices (glue for attaching cells)

matricellular protein found in basement membranes

• Receptors for fibronectin, laminins, CCN proteins as well as other molecules; often connect to cell signaling and cytoskeletal machinery via tightly complexed proteins on cytoplasmic side of membranes
• •"they're everywhere"

• •clinical correlate: integrin
• •defect of integrins in platelets; inability to clot properly
• •autosomal recessive

major component of the elastic laminae of large artery walls; cross-linked by fibrillin

• •clinical correlate: elastin
• •defective fibrillin fails to cross-link elastin
• •people with Marfan's are really tall --> seen in a few basketball players
• •upon overexertion aneurism can occur in athletes with Marfan's

• cell adhesion molecules important in maintaining tissue integrity (ie, skin) by connecting desmosomes of adjacent skin cells (require Ca 2+)
• •defects in cadherins connecting desmosomes can weaken/destroy integrity of the skin and cause sloughing and blistering
• •(critical in embryonic development)

• •autoimmune blistering disease, therefore clinical correlate: cadherins
• •antibodies against cadherins destroy desmosomes and hemidesmosomes, resulting in blisters

• •basically play a role in bringing immune response to an infected EC
• •leukocytes roll along endothelium by sticking weakly to P-selectin (a matricellular protein)
• •if a tissue is inflamed, the endothelial cells in that area express Platelet Activating Factor (PAF), which binds to the PAF receptor ON the leukocyte --> stronger binding
• •this binding additionally activates an integrin ON the leukocyte which itself binds tightly to ICAM-1 back to the EC membrane
• •leukocyte stops and invades the tissue

• enzymes in the matrix that bind metal ions and are responsible for breaking down collagen and the ECM
• •required for stimulating and inhibiting angiogenesis, cancer cell metastasis, tissue remodeling, & wound healing

• clinical correlate: MMPs (+ fibronectin, laminin, matrix-degrading enzymes)
• •cancer that has spread from the place where it first started to another place in the body

cell-matrix interactions

related to most things discussed in CellBio proteoglycans, CAMs, etc)