Cell-Matrix Interactions

Question 1

Cell Differentiation

Answer 1

• cells select different genes to express
• cells make decisions
• cells have memory

Question 2

What is wound healing?

Answer 2

• cells de-differentiate
• cells proliferate
• cells revert

Question 3

Epithelial Cells

Answer 3

• in epidermis
• spindle orientation
• tightly bound
• cell-cell adhesions

Question 4

Fibroblasts

Answer 4

• in dermis
• leading/lagging edge
• NO cell-cell adhesions

Question 5

Cell Junctions

Answer 5

• anchoring
• occluding
• communicating

Question 6

Focal Adhesions

Answer 6

Actin cytoskeleton + Integrins
- transient
- actin uses to migrate

Question 7

Hemi-desmosomes

Answer 7

Intermediate Filaments + Integrins
- stable

Question 8

What is the structure of collagen?

Answer 8

• α-chain (insoluble trimeric structure)
• homo-trimeric or hetero-trimeric
  1) mostly hydroxy-proline/hydroxy-lysine
  2) mostly proline
  3) glycine

Question 9

4 Characteristics of Collagen and their Types?

Answer 9

Fibrillar = Type I and II (bone, skin)
Fibril-Associated = Type VII (dermis)
Sheet-Forming = Type IV and VI (basal lamina)
Transmembrane = Type XII (hemi-desmosomes)

Question 10

How to transmit info from ECM to nucleus?

Answer 10

• Integrins (PM TM protein)
• Talin + Vinculin (Adapter proteins)
• Actin cytoskeleton
• Nesprin 1+2 (Adapter proteins)
• Lamins (Nuclear structural proteins)

Question 11

How does collagen assemble?

Answer 11

• Post-translational modification (hydroxylation and glycosylation)
• Pro-collagen assembly = triple helix
• Pro-collagen processing = cleave C and N terminal
• Fibrillogenesis = cross-linking — only in fibrillar

Question 12

Collagen-related diseases?

Answer 12

• Scurvy = lack of vitamin C at post-translational modify
• Osteogenesis Imperfecta = problem at pro-collagen assembly
• Ehlers-Danlos = problem at pro-collagen processing

Question 13

What are proteoglycans?

Answer 13

• specialized repeating sugars attached to protein core

Question 14

Glycosaminoglycans (GAGs)

Answer 14

• Chondroitin Sulphate
• Keratan Sulphate
• Heparan Sulphate
• Hyaluronate

Question 15

What is the synthesis of proteoglycans?

Answer 15

• protein core made in RER
• GAGs added in Golgi
  — Enzymatic reaction: xylose added on serine

Question 16

What are Multi-Adhesive Proteins?

Answer 16

• long, flexible macromolecules
• attach cells to ECM by cross-linking
  (Fibronectin + Laminin)

Question 17

Types of Integrins?

Answer 17

α1β1 = collagen
α3β1= laminin
α5β1 = fibronectin (fibroblasts)
α6β4 = laminin (epithelial cells)

Question 18

3D Cell Culture

Answer 18

• transfer epithelial cells to living stroma (ECM + fibroblast)
• layers of epithelial cells
• induce them to be tumourgenic
  – epidermis gets thicker and cells migrate into dermis

Question 19

What is Epidermis Bullosa?

Answer 19

• epidermal fragility
• mutation in: IF or integrin gene or collagen

Question 20

Heterophillic vs Homophillic Cell-Adhesion Molecules

Answer 20

Heterophillic
- integrins, selectins, Ig-Superfamily
Homophillic
- Ig-Superfamily, cadherins

Question 21

What are Selectins?

Answer 21

• found in platelets
• carbohydrate binding
• divalent cation dependent (open binding site)

Question 22

What are types of selectins?

Answer 22

E-selectin (endothelial)
L-selectin (leukocyte)
P-selectin (platelet)

Question 23

What are Ig-Superfamilies?

Answer 23

• calcium independent
• immunoglobulin domains
• Homophillic = 2 same vs Heterophillic = 2 diff

Question 24

What are cadherins? What are the types of cadherins?

Answer 24

• calcium dependent
• lateral vs intercellular

E-cadherin (epithelial)
N-cadherin (neural)
P-cadherin (placental)

Question 25

What are the properties affecting cell-cell adhesion strength?

Answer 25

• binding affinity (strength)
• spatial distribution (volume)
• activity state (phosphorylation?)
• external forces (stress)