L2 Extracellular Matrix

What is the Extracellular Matrix (ECM)?

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

What are the macromolecules present in the ECM?

proteins, polysaccharides, minerals that provides a scaffold for cell attachment and transmits chemical messengers to cells

What is the purpose of ECM?

helps hold tissue together, supports plasma membrane

Is ECM the same all over the body?

no, varies per tissue

How does Connective Tissue differ from ECM?

fewer cells per volume than ECM

What is the purpose of connective tissue?

provides strength, protection, and elasticity

What are some examples of connective tissue?

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

What are the 3 major categories of extracellular macromolecules in the ECM?

Glycosaminoglycans (GAGs) & Proteoglycans, Fibrous Proteins, Adhesive Proteins

What are Proteoglycans?

aggregates of GAG and Proteins

What is the chemical structure of GAGs?

repeating Disaccharide chains where one of the sugars are N-acetylated amino sugar

What is the most prevalent GAG?

Chondroitin Sulfate; other examples: Hyaluronic Acid, Keratin Sulfate, Dermatan Sulfate, Heparin, Heparan Sulfate

What makes up Proteoglycan Monomers?

core protein with GAG chains

what makes up cartilage proteoglycans?

GAGs that include chondroitin sulfate and keratin sulfate

how does a proteoglycan aggregate form?

the binding of individual proteoglycan monomers with a large hyaluronic acid GAG

How do Glycosaminoglycans help with joints?

helps lubricate joints

What are the OTC dietary supplements that can reduce swelling and pain for osteoarthritis?

Glucosamine and Chondroitin

What are the components of Fibrous Proteins?

specific types of amino acids

What are the 2 major fibrous proteins in the ECM?

Collagen & Elastin

what are collagen and elastin are components of?

tissue, skin, and blood vessel walls

What is the most abundant protein in the human body?

collagen; ~30% total body protein mass

In which tissues is collagen the main type of protein?

Bone, Tendon, Skin

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)

Which amino acids are abundant in collagen?

Proline (Pro) & Lysin (Lys)

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

Hydroxylation reactions; requires Oxygen, Ferrous Iron (Fe++), and Vitamin C (Ascorbic Acid)

What are the types of Collagen where 90% resides in the body?

Fibril forming: Type I: Skin, Bone, Tendon, Blood Vessels, Cornea; Type II: Cartilage, Intervertebral Disk, Vitreous Body; Type III: Blood Vessels, Skin, Muscle;

Network forming: Type IV: Basement Membrane

What can cause changes in skin structure?

Low Collagen

How does aging affect collagen fibers?

aging results in rigid collagen fibers and form wrinkles

What slows down collagen damage?

Antioxidants which inhibits free radicals

What stimulates new collagen fibers production in the skin?

Retinoic Acid

What amino acids are abundant in Elastin?

Glycine, Alanine, Proline, Lysine, and Hydroxyproline

What is the precursor for Elastin?

Tropoelastin

What type of linkage does Tropoelastin use to connect the elastin monomers?

Desmosine Cross-Link; allows Elastin to stretch

What happens to Lysyl side chains in Tropoelastin?

modified to become Allysyl Side Chains

With which Glycoprotein Microfibrils does Tropoelastin interact?

Fibrillin

What are 4 examples of diseases related to fibrous proteins?

Scurvy, Less Collagen, Ehlers-Danlos Syndrome, Marfan Syndrome

What is Scurvy?

Vitamin C Deficiency; Hydroxylation cannot occur, resulting in unstable triple helices and bleeding gums

What effects can occur due to less collagen?

reduced tissue strength & stability, fragile blood vessels, bruising, slow wound healing, gingival hemorrhage, and tooth loss

What is Osteogenesis Imperfecta?

“Brittle Bone Disease”; Mutation in Collagen Gene; Abnormal Type I Collagen

What is Ehlers-Danlos Syndrome?

defective structure, production, or processing of Fibrillar Collagen; stretchy skin

What is Marfan Syndrome?

mutation in gene that codes Fibrillin-1 protein that maintains elastin fibers; affects Aorta, Ligaments, and Eye; symptoms include tall stature, scoliosis, abnormal joint mobility, and hyperextensibility of hands, feet, elbows, and knees

What are Cell Adhesion Molecules?

cell-surface proteins that allow cells to adhere with each other in ECM

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

Fibronectin (connective tissues) and Laminin (epithelial tissues)

What are the 4 families of Adhesion Molecules?

Cadherins, Selectins, Immunoglobulin Superfamily, Integrins

What is the role of Cadherins?

holds cells together for tissue integrity

What is the role of Selectins?

WBC migration to sites of inflammation

What is the role of the Immunoglobulin Superfamily?

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

What is the role of Integrins?

Alpha & Beta chains; adhesion of Leukocytes, helps anchor cells to ECM, relays signals from ECM to cells

What are some examples of adhesion molecule defects?

Epithelial-Mesenchymal Transition (EMT), Metastasis (tumor spreading), Pemphigus

What is Epithelial-Mesenchymal Transition (EMT)?

when epithelial cells undergo changes in adhesion and polarity; occurs in embryogenesis and cancer progression

What is metastasis in terms of adhesion molecule defects?

loss of E-cadherin-mediated cell to cell adhesion

What is Pemphigus?

Autoimmune condition; disruption of Cadherin-Mediated Cell Adhesions; Auto-Abs bind to proteins in Cadherins subfamily; causes blistering conditions

What happens with increased adhesion molecule expression and inflammation?

Asthma (increased ICAM-1 expression), Rheumatoid Arthritis, Infection (adhesion molecules assist in viral infection)