Extracellular Matrix

Question 1

What is the ECM?

Answer 1

Filler and macromolecules (secreted by the cell)

Question 2

Functions of ECM

Answer 2

1. Cellular division
2. Motility
3. Differentiation
4. Adhesion
5. Structure

Question 3

3 classes of ECM components

Answer 3

1. Structural proteins
2. Proteoglycans
3. Adhesive glycoproteins

Question 4

Examples and functions of structural proteins

Answer 4

Collagens and elastins → provide strength and flexibility

Question 5

Proteoglycans

What are they:

Function:

Answer 5

Protein-polysaccharide complexes

Provide matrix for structural proteins

Question 6

Examples and function of adhesive glycoproteins

Answer 6

Fibronectins and laminins → attach cells to matrix

Question 7

______ is the most abundant protein in vertebrates and it contains __% of total body protein

Answer 7

Collagen → 25-30%

Question 8

Tendons and ligaments contain a lot of?

Answer 8

Collagen

Question 9

Collagen structure

Answer 9

Rigid triple helix of polypeptide chains

Question 10

Collagen strength

Answer 10

1 mm fiber can hold 20 lbs

Question 11

__ different alpha chains combine to form __ types of collagen

Which are most abundant?

Answer 11

25 different alpha chains → 15 types of collagen

I, II and III most abundant

Question 12

Type I composes __% of collagen in body

Answer 12

90%

Question 13

Collagen cross linking function

Answer 13

Strengthens collagen bundle to withstand high stress

Question 14

Elastin provides flexibility to what tissues?

Answer 14

1. Lungs
2. Heart
3. Arteries
4. Skin
5. Intestines
6. Ears

Question 15

Elasticity is dependent on what ratio?

Answer 15

Collagen : Elastin

Question 16

Elastin composition

Answer 16

Proteins rich in glycine and proline (no hydroxylation) and elastin molecule (crosslinked between lysines)

Question 17

Proteoglycan composition

Answer 17

Glycoprotein + glycosaminoglycan side chain

Question 18

GAGs

Answer 18

Long polysaccharides → 2 monosaccharides in alternating order

Question 19

Glycoprotein

Answer 19

Protein with GAGs (up to 95% carbohydrate)

Question 20

How are proteoglycans classified?

And what are 3 of the most common?

Answer 20

By glycosaminoglycan side chain:

1. Chondroitin sulfate
2. Keratan sulfate
3. Heparin / heparin sulfate

Question 21

Location of chondroitin sulfate

Answer 21

Cartilage (osteoarthritis implications)

Question 22

Keratan sulfate locations and function

Answer 22

1. Cornea
2. Cartilage
3. Bone

Cushion

Question 23

Proteoglycan functions

Answer 23

1. Receptors
2. Filtration
3. Shock absorption
4. Trap water (>50%x their weight)

Question 24

Hyaluronate functions:

Answer 24

1. Lubricates joints

2. Found on surface of migrating cells → facilitates cell migration

Question 25

Heparan sulfate What is it: Location:

Answer 25

Family with side chains made of D-glucosamine or L-iduronic acid Found in every cell of body

Question 26

Heparin What is it: Function:

Answer 26

One member of the heparan sulfate family Anticoagulant

Question 27

Heparan sulfate family functions (other than heparin)

Answer 27

1. Bind growth factors 2. Important role in inflammation 3. Entry of virus into cells (herpes, rabies)

Question 28

Fibronectin

Answer 28

Most common adhesive glycoprotein (contains about 5% carbohydrates) Family of closely related proteins

Question 29

Fibronectin solubility

Answer 29

Can be soluble, insoluble or partialy soluble → caused by alternative splicing of the same gene

Question 30

Fibronectin roles

Answer 30

1. Maintain cell shape 2. Possible role in cancer 3. Blood clotting (soluble form) 4. Wound healing → guides immune cells to wound 5. Cell migration

Question 31

Laminins are mainly located where?

Answer 31

Basal laminae

Question 32

Basal lamina

Answer 32

Separates ECM from epithelial cells

Question 33

Basal lamina roles

Answer 33

1. Structural support 2. Permeability barrier (acts as filter in kidney) 3. Cell migration (may allow migration of cancer cells)

Question 34

Matrix remodeling is most active at?

Answer 34

Sites of abundance-cellular sources: 1. Cartilage: chondrocytes 2. Bone: osteocytes, osteoblasts 3. Tendon: teniacytes (fibrocytes) 4. Cornea: fibrocytes

Question 35

Enzymes which degrade ECM

Answer 35

1. Metalloproteinases | 2. Serine proteases:

Question 36

2 ways to stop ECM degradation

Answer 36

1. Tissue inhibitors of metalloproteinases (TIMP1, 2, 3, 4) → ireversible 2. Serine protease inhibitors

Question 37

Polypeptide chains found in collagen are high in?

Answer 37

1. Glycine 2. Hydroxylysine 3. Hydroxyproline

Question 38

Metalloproteinases

Answer 38

Specific for 1 ECM component Requires zinc or calcium

Question 39

Serine proteases

Answer 39

Cleave protein sequences at serine residues → work with metalloproteinases

Question 40

Fibronectin's role in cancer

Answer 40

Carcinomas are unable to synthesize fibronectins → cell detaches from ECM

Question 41

Type I collagen is found where?

Answer 41

1. Skin 2. Bones 3. Tendons 4. Ligaments

Question 42

Collagen cross linking with aged animals

Answer 42

Can become abnormal → loss of joint function

Question 43

2 forms of hyaluronate

Answer 43

Proteoglycan (backbone in cartilage) or free molecule

Question 44

Basal lamina surrounds what types of cells?

Answer 44

1. Muscle 2. Fat 3. Schwann cells

Question 45

Composition of basal lamina

Answer 45

Thin sheet (50 nm) of EC material