ECM And Cell Adhesion

Question 1

Does CT or epithelial tissue have more ECM and less cells?

Answer 1

CT, epithelium is opposite

Question 2

GAGs and relation to water

Answer 2

. Repeating disaccharide units w/ negative charges ( acidic sugar and N-acetylated amino sugar)
. H2) floods into ECM w/ GAGs bc of neg. charge causing swelling pressure (turgor) allowing ECM to resist tissue compression forces

Question 3

Formation of proteoglycan monomers

Answer 3

. Core protein w/ GAGs covalently bonding extending out from it

Question 4

What do individual proteoglycan monomers associate w/?

Answer 4

Hyaluronic acid

Question 5

Percentage of protein mass made up of collagen?

Answer 5

25%

Question 6

Collagen fiber structure

Answer 6

. Collagen molecules made up of 3 chains (alpha chains) that wind around each other
. Every 3rd amino acid is Gly allowing tight packing
. Packaging of collagen molecules w/in fibrils leads to repeating structure w/ a banding pattern

Question 7

Synthesis of collagen

Answer 7

. Individual collagen polypeptide chains are translated on membrane-bound ribosomes
. Selected Pro and Lys hydroxylated (dependent on Vit. D)
. Some hydroxylysine residues are glycosylated
. Triple helix forms
. Excreted into ECM and propeptides cleaved to yield tropocollagen
. Mature collagen formed from cross linking of tropocollagen

Question 8

Cross-linking of collagen fibrils

Answer 8

.allysyl residues formed on fibrillar array acted on by lysyl oxidase allowing them to form covalent cross links seen in mature collagen fibers

Question 9

Cross linking function

Answer 9

Tensile strength for proper functioning CT

Question 10

Elastin structure

Answer 10

. Has small, nonpolar amino acid residues (Gly, Ala, Val)
. Rich in Pro and Lys but little hydroxyproline and NO hydroxylysine
. not glycoprotein
. Not triple helical
. Some side chains of Lys modified to form allysine
. 3 allysine residues and side chain of 1 unaltered Lys joint together covalently to form desmosine cross link

Question 11

Elastin modifications once excreted into ECM

Answer 11

. Tropoelastin (new elastin in ECM) interacts w/ glycoprotein microfibrils (fibrillin) that serve as scaffolding onto which tropoelastin is deposited
. Side chains of Lys residues of tropoelastin modified to form allysine residues
. 3 alysyl residues and side chain of 1 unaltered Lys residue joined together covalently to form desmosine cross link

Question 12

Where are fibronectin and laminin found?

Answer 12

Fibronectin: CT
Laminin: epithelial tissues

Question 13

Binding domains of fibronectin and laminin

Answer 13

Cell, collagen, and proteoglycans

Question 14

How are many simple tissues derived from?

Answer 14

precursor cells whose progeny are prevented from wandering away by being attached to ECM, other cells, or both

Question 15

What is selective adhesion essential for?

Answer 15

.development of tissues that have complex origins involving migration

Question 16

Cell junctions

Answer 16

. Occluding (tight): form physical barrier
. Anchoring (desmosome): couple neighboring cells to each other or to ECM through interactions mediated by cytoskeleton
. Communicating (gap): attach cells to allow signal transfer

Question 17

Families of adhesion molecules

Answer 17

. Cadherin
. Selectins
. Immunoglobulin superfamily
. Integrin

Question 18

Cadherins

Answer 18

. Mediate Ca-dependent cell-cell adhesion by homophilic mechanism
. Transmembrane linker proteins that mediate interactions btw actin of the cytoskeleton of the cells they join together
. Play role in holding cells and maintaining tissue integrity

Question 19

Selectins

Answer 19

. Cell-surface-carbohydrate-binding proteins that mediate heterophilic binding
. Function in transient cell-cell adhesion interactions, important in bloodstream
. Enables WBCs to bind endothelial cells and migrate to sites of inflammation

Question 20

Immunoglobulin Superfamily

Answer 20

. Mediate Ca-independence cell-cell adhesion by homophilic or heterophilic binding
. Transient expression during development implicating a role for these ,ole clues in development
. Cell-cell adhesion mediated is weaker than adhesion by cadherins
. Contribute to regulation or fine-tuning of adhesive interactions during development and regeneration

Question 21

Integrin

Answer 21

. Adhesion molecules consisting of alpha and beta transmembrane chains important for cell-matrix and cell-cell adhesion
. Beta 2 type of beta subunit expressed only on leukocytes to participate in cell-cell interactions through integrin binding to other adhesion molecules on other cells
. Mediate bidirectional interactions btw cytoskeleton and ECM
. Most connect to bundles of actin
. Cytoplasmic portion interacts w/ cytoskeletal components and it important for transmission of signals btw inside and outside of cell

Question 22

T/F integrins bind ligand with low affinity

Answer 22

T, attachment of cells to ECM depends on multiple weak adhesions

Question 23

T/F Integrins with different alpha and beta chains have different binding properties

Answer 23

T

Question 24

different alpha and beta chains

Answer 24

14 alpha

8 beta

Question 25

Fatty streak

Answer 25

. 1st pathological changes in atherosclerosis

. Located on tunica intima

Question 26

Process of extravasation

Answer 26

. Rolling
. Triggering
. Arrest/Firm adhesion
. Diapedesis

Question 27

What is extravasation mediated by and how?

Answer 27

Adhesion molecules

. Monocytes binds to ligand (member of Ig superfamily) on surface of endothelial cell to roll

Question 28

What is activated during cell triggering in extravasation

Answer 28

. Integrins on monocyte are activated and firm arrest monocyte

Question 29

What follows stable arrest and what molecules are involved?

Answer 29

. Diapedesis

. Same integrins in arrest participate in trans endothelial migration in conjunction w/ other adhesion receptors

Question 30

After diapedesis what steps occur in cardiovascular disease?

Answer 30

. Macrophages consume excess modified (oxidized) lipoprotein becoming foam cells
. Foam cells accumulate and release growth factors that stimulate proliferation of smooth muscle and calcification of plaque

Question 31

Receptors on foam cell

Answer 31

. Low affinity non-specific scavenger receptors take up modified LDL (oxLDL)
. High affinity receptors specific for LDL becomes downregulated when cell has sufficient cholesterol

Question 32

LDL to oxLDL reaction

Answer 32

. LDL oxidized w/ oxidants, Vit. E, beta-carotene, ascorbic acid to oxLDL

Question 33

What can help w/ joint health?

Answer 33

Glucosamine

Question 34

Where are individual fibrillar collagen polypeptide chains translated?

Answer 34

Membrane bound proteins (rER)

Question 35

Tropocollagen

Answer 35

Collagen that is excreted into ECM before cross-linking

Question 36

Scurvy

Answer 36

. Vit. C deficiency
. Lack of hydroxylation of Pro and Lys causing defective pro-alpha chains so you cannot form a stable triple helix and immediately degrade in cell
. Only new collagen is affected

Question 37

Scurvy symptoms

Answer 37

. Blood vessels fragile 
. Bruising
. Wound healing slows
. Tooth loss occurs
. Fractures can happen but not common in adults 
. Mimic child abuse signs in children

Question 38

Osteogenesis Imperfecta

Answer 38

. Abnormal collagen type I production
. Most common type is type I where there’s low concentration of collagen of normal structure
. Type II is lethal

Question 39

Mutation in Marian syndrome

Answer 39

. Fibrillin-1 (FBN1) causes alpha1-antitrypsin deficiency

. FBN1 defective causes inc. in TGF-beta)

Question 40

Alpha-antitrypsin deficiency

Answer 40

. Normally keeps neutrophil elastase destruction in check to prevent damage to normal lung elastin
. W/ deficiency there is dec. inhibition and lung tissue cannot regenerate

Question 41

Pemphigus

Answer 41

. Autoimmune blistering disease related to adhesion

. Autoantibodies develop against cadherins, disrupting their interactions