L2 Extracellular Matrix

Objectives

  • Define Extracellular Matrix (ECM)

  • Discuss the Macromolecules present in the ECM '

  • Discuss the Disorders Associated with the Deficiency of Fibrous Proteins

  • Discuss Cell-Adhesion Molecules

  1. What are the 4 different types of tissues mentioned

    • Epithelial, Muscle, Nervous, Connective

  2. Which 3 are composed principally of Cells

    • Epithelial

      • covers entire body surface

      • first line of defense

      • used for protection, secretion, absorption, and filtration

    • Muscle

      • used for motion and contraction

    • Nervous

      • conducts impulses to control muscles, mental activity, and bodily functions

  3. What is the ECM?

    • network of proteins and molecules that surround, support, and give structure to cells and tissues

  4. What does the ECM contain?

    • proteins, polysaccharides, minerals

      • provides a scaffold for cell attachment

      • transmits chemical messengers to cells

  5. What is the purpose of ECM

    • helps hold tissue together

    • supports plasma membrane

  6. Is ECM the same all over the body?

    • no, varies per tissue

  7. Why is Connective Tissue different from ECM?

    • fewer cells per volume than ECM

  8. What is the purpose of connective tissue? What are some examples?

    • provides strength, protection, and elasticity

    • blood, bone, cartilage, fat, ligaments, lymph, tendons

    • contains many macromolecules in extracellular space

  9. What are the 3 major categories of extracellular macromolecules in the ECM

    1. Glycosaminoglycans (GAGs) & Proteoglycans

    2. Fibrous Proteins

      • Collagen & Elastin

    3. Adhesive Proteins

      • Fibronectin & Laminin

  10. What are Proteoglycans

    • aggregates of GAG and Proteins

  11. What are GAGs mostly made of chemical structure-wise

    • repeating Disaccharide chains

  12. What is the most prevalent GAG? What are other examples?

    • Chondroitin Sulfate

    • Hyaluronic Acid (polymer of disaccharides), Keratin Sulfate, Dermatan Sulfate, Heparin, and Heparan Sulfate

  13. What makes up Proteoglycan Monomers

    • core protein with GAG chains

  14. How does Glycosaminoglycans help with joints?

    • helps lubricate joints

  15. What was the examples given as OTC dietary supplements that can be used to reduce swelling and pain such as for osteoarthritis

    • Glucosamine and Chondroitin

  16. What are the components of Fibrous Proteins

    • specific types of amino acids

  17. What are the 2 major fibrous proteins in the ECM?

    • Collagen & Elastin

  18. What is the most abundant protein in the human body ~30% total body protein mass?

    • collagen

  19. Where is collagen the main type of protein?

    • Bone, Tendon, Skin

  20. What is the structure of collagen

    • Three Helical Polypeptide Alpha Chains of Amino Acids

    • Repeating units of X-Y-Gly

      • X is Proline

      • Y is a modified form of Proline or Lysine

  21. What specific amino acids were mentioned is abundant in collagen?

    • Proline (Pro) & Lysin (Lys)

  22. What type of reaction occurs for the synthesis of collagen? What are the required molecules needed?

    • Hydroxylation reactions

    • Oxygen, Ferrous Iron (Fe++), and Vitamin C (Ascorbic Acid)

  23. List the types of Collagen where 90% resides in the body?

    • Type I

      • Skin, Bone, Tendon, Blood Vessels, Cornea

    • Type II

      • Cartilage, Intervertebral Disk, Vitreous Body

    • Type III

      • Blood Vessels, Skin, Muscle

    • Type IV

      • Basement Membrane

  24. What can cause changes in skin structure?

    • Low Collagen

  25. How does aging affect collagen fibers?

    • aging results in rigid collagen fibers

  26. What slows down collagen damage?

    • Antioxidants

  27. What stimulates new collagen fibers production in the skin?

    • Retinoic Acid

  28. What amino acids are abundant in Elastin?

    • Glycine, Alanine, Proline, Lysine, and Hydroxyproline

  29. What is the precursor for Elastin?

    • Tropoelastin

  30. What type of linkage does Tropoelastin has to connect the elastin monomers?

    • Desmosine Cross-Link

      • allows Elastin to stretch

  31. Tropoelastin has Lysyl side chains that are modified to become what type of side chains?

    • Allysyl Side Chains

  32. Tropoelastin interacts with what Glycoprotein Microfibrils?

    • Fibrillin

  33. What 4 examples were mentioned in relation to diseases related to fibrous proteins?

    1. Scurvy

      • Vitamin C Deficiency

      • Hydroxylation cannot occur

      • unstable triple helices

      • Bleeding gums

    2. Insufficient Collagen

      • reduced strength and stability in tissue

      • fragile blood vessels → bruising & slow wound healing

      • Gingival Hemorrhage & Tooth Loss

      • Osteogenesis Imperfecta: “Brittle Bone Disease”

        • Mutation in Collagen Gene

        • Abnormal Type I Collagen

    3. Ehlers-Danlos Syndrome

      • defective structure, production, or processing of Fibrillar Collagen

      • Stretchy Skin

    4. Marfan Syndrome

      • mutation in gene that codes Fibrillin-1 which is essential for elastin fiber maintenance

      • affects Aorta, Ligaments, and Eye

      • Tall stature, scoliosis, abnormal joint mobility, elongated finger/arm bones, and hyperextensibility of hands, feet, elbows, and knees

  34. What cell-surface proteins that allows cells adhere with each other in ECM?

    • Cell Adhesion Molecules

  35. What Adhesive Glycoproteins are secreted by cells in the extracellular space?

    • Fibronectin

      • connective tissues

    • Laminin

      • epithelial tissues

  36. What are the 4 families of Adhesion Molecules?

    1. Cadherins

      • holds sells together for tissue integrity

    2. Selectins

      • WBC migration to sites of inflammation

    3. Immunoglobulin Superfamily

      • facilitate adhesion of Leukocytes to Endothelial Cells that line blood vessels during injury or stress

    4. Integrins

      • Alpha & Beta chains

      • Adhesion of Leukocytes

      • helps anchor cells to ECM

      • relays signals from ECM to cells

  37. What 3 examples occur due to adhesion molecule defects?

    1. Epithelial-Mesenchymal Transition (EMT)

      • when epithelial cells undergo changes in adhesion and polarity

      • occurs in embryogenesis and cancer progression

    2. Metastasis (tumor spreading)

      • loss of E-Cadherin-mediated cell to cell adhesion

    3. Pemphigus

      • Autoimmune condition

      • disruption of Cadherin-Mediated Cell Adhesions

      • Auto-Abs bind to proteins in Cadherins subfamily

      • blistering conditions

  38. What are 3 examples when there is increases adhesion molecule expression and inflammation

    1. Asthma

      • increased ICAM-1 (intercellular adhesion molecule 1) expression in respiratory tract

    2. Rheumatoid Arthritis

      • bone cells may have increases expression of adhesion molecules

    3. Infection

      • adhesion molecules assist in viral infection