ECM and cell adhesion

Question 1

Which macromolecules are found in the ECM?

Answer 1

fibrous proteins and glycosaminoglycans

Question 2

What makes the ECM so different in various tissues?

Answer 2

1. The diveristy of proteins and carbohydrate components of the ECM

Question 3

List the different functions of the ECM

Answer 3

1. Adhesive substrate (tracks to direct migratory cells)
2. Provides structure (tissue bounderies)
3. Presents growth factors to there receptors
4. stores growth factors
5. senses and transduces mechanical signals

Question 4

Which parts of tissues make up the ECM?

Answer 4

interstitial matrix and basement membrane

Question 5

How does the ECM resist compression?

Answer 5

polysaccharide gels and fibrous proteins fill the interstitial space

Question 6

What percentage of the total proteins in the body does collagen form?

Answer 6

25%

Question 7

What is the structure of collagen?

Answer 7

Triple helical structure formed by 3 peptide chains.
Every third amino acid is glycine, the smallest side chain able to fit into the crowded central core.

Has a Gly-X-Y sequence. X and Y can be any acid but X is often proline and Y is hydroxyproline.

Question 8

Describe the function and location of Fibillar collagens

Answer 8

Function- Provide tensile strength

Location- tendons,ligmanets,skin

Question 9

Describe the function and location of non-Fibillar collagen?

Answer 9

Function- Lattice-forming. Major structural component of basment membranes

Question 10

What are basement membarnes? What is there function?

Answer 10

Thin layers of ECM
Function- Anchor cells to surrounding connective tissue
-Filtration

Question 11

What is the function of collagen V?

Answer 11

Regulates the diameter of collagen type 1 fibrils

Question 12

What is Osteogenesis imperfecta?

Answer 12

Brittle bone disease
Caused by mutations affecting the synthesis of type 1 collagen

Mutations mainly single base substitutions which convert glycine in the Gly-X-Y to a bulky amino acid preventing the correct folding of the collagen fibers into triple helix

Question 13

Why are bones most affected in Osteogenesis imperfecta (brittle bone disease)

Answer 13

Collagen type 1 is dominant in bone

Question 14

Which protein is predominant in elastic fibers?

Answer 14

Elastin

Question 15

What makes elastin flexible?

Answer 15

Weak hydrophobic interactions between valine residues

Question 16

Name 1 similarity and 2 differences between collagen and elastin?

Answer 16

Similarity- both rich in glycine and proline
Differences- elastin is more hydrophobic
In elastin 1 in seven is valine

Question 17

Which glycoprotein covers Elastin?

Answer 17

Fibrillin

Question 18

What causes marfan syndrome? Name 2 symptoms

Answer 18

Mutation in fibrillin gene
Tall stature, long arms and legs, loose joints, deformed spine. Floppy mitral vaalve and the arotic walla is prone to rupture

Question 19

What are the 2 main sugar containing proetins?

Answer 19

Glycoproteins and proteoglycans

Question 20

What are the functions of glycoproteins?

Answer 20

• receptors for hormones
• cell-cell intercations
• provide strength and support to ECM

Question 21

What are proteoglycans?

Answer 21

Gel forming part of the ECM

Composed of petide chinas and carbohydrates

Question 22

What is the function of proteoglycans?

Answer 22

provide structural support to tissues, especially cartilage and connective tissue

Question 23

Describe the sturcture of the proteoglycan found in cartilage

Answer 23

Large aggregates composed of chondroitin sulfate and keratin sulfate chains linked to core proteins form a jelly like matrix

Question 24

How does water enter the ECM?

Answer 24

Because of the negtaive charge of proteoglycans, counter ions are required to maintain electrical neutrality. These ions draw water into the ECM. Causing the matrix to swell and stiffen. = tension between osmotic forced and binding interactions between proteoglycans and collagen

Question 25

What do proteoglycans do to growth factors?

Answer 25

The control the bio-avalibility and store them

Question 26

Which cellular processes are regulated by cell adhesion?

Answer 26

- Signal transdution (cells detect and respond to change) - cell migration - tissue development

Question 27

What is the name used for cell adhesion molecules? State all the different types

Answer 27

CAMS | integrins, immunoglobulin (Ig) superfamily, cadherins, and selectins

Question 28

Which CAMS are homophilic and heterophilic?

Answer 28

Homophilic- Cadherins and immunoglobulins (bind to the same type of CAM) Heterophilic- integrins and selectins (bind to different types of CAMS)

Question 29

What are intergrins?

Answer 29

Plasma membrane proteins which transmit mechanical signals between the ECM and intracellular space

Question 30

Which factors help guide cell migration?

Answer 30

External signals- - chemical signals - Mechanical signals

Question 31

What happens if a cell migrates on a flat substrate without ECM?

Answer 31

Detachment and apoptosis

Question 32

Describe the 4 stages in cell migration

Answer 32

1. Polymerization of actin filaments at leading edge gives a protrusive force. 2. New adhesions are rapidly linked to the actin filaments. 3. Retrograde actin movment and contractile foces pull cell body forward 4. Contractile network forces and actin filaments retract the tailing cell edge

Question 33

What is Leukocyte extravasation?

Answer 33

The movement of leukocyte into the cell caused by infection or inflammation. Leukocyte binds to ICAM-1 which stops it rolling and starts migrating into the injured cell

Question 34

What helps cancers metastasis?

Answer 34

Cleavage if cell adhesion occurs. e.g. Cadherins inactivated via genetic mutation Activation of growth factors and cytokines also helps them migrate