Cell-Matrix Interactions Flashcards
Cell Differentiation
- cells select different genes to express
- cells make decisions
- cells have memory
What is wound healing?
- cells de-differentiate
- cells proliferate
- cells revert
Epithelial Cells
- in epidermis
- spindle orientation
- tightly bound
- cell-cell adhesions
Fibroblasts
- in dermis
- leading/lagging edge
- NO cell-cell adhesions
Cell Junctions
- anchoring
- occluding
- communicating
Focal Adhesions
Actin cytoskeleton + Integrins
- transient
- actin uses to migrate
Hemi-desmosomes
Intermediate Filaments + Integrins
- stable
What is the structure of collagen?
- α-chain (insoluble trimeric structure)
- homo-trimeric or hetero-trimeric
1) mostly hydroxy-proline/hydroxy-lysine
2) mostly proline
3) glycine
4 Characteristics of Collagen and their Types?
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)
How to transmit info from ECM to nucleus?
- Integrins (PM TM protein)
- Talin + Vinculin (Adapter proteins)
- Actin cytoskeleton
- Nesprin 1+2 (Adapter proteins)
- Lamins (Nuclear structural proteins)
How does collagen assemble?
- 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
Collagen-related diseases?
- Scurvy = lack of vitamin C at post-translational modify
- Osteogenesis Imperfecta = problem at pro-collagen assembly
- Ehlers-Danlos = problem at pro-collagen processing
What are proteoglycans?
- specialized repeating sugars attached to protein core
Glycosaminoglycans (GAGs)
- Chondroitin Sulphate
- Keratan Sulphate
- Heparan Sulphate
- Hyaluronate
What is the synthesis of proteoglycans?
- protein core made in RER
- GAGs added in Golgi
— Enzymatic reaction: xylose added on serine
What are Multi-Adhesive Proteins?
- long, flexible macromolecules
- attach cells to ECM by cross-linking
(Fibronectin + Laminin)
Types of Integrins?
α1β1 = collagen
α3β1= laminin
α5β1 = fibronectin (fibroblasts)
α6β4 = laminin (epithelial cells)
3D Cell Culture
- 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
What is Epidermis Bullosa?
- epidermal fragility
- mutation in: IF or integrin gene or collagen
Heterophillic vs Homophillic Cell-Adhesion Molecules
Heterophillic
- integrins, selectins, Ig-Superfamily
Homophillic
- Ig-Superfamily, cadherins
What are Selectins?
- found in platelets
- carbohydrate binding
- divalent cation dependent (open binding site)
What are types of selectins?
E-selectin (endothelial)
L-selectin (leukocyte)
P-selectin (platelet)
What are Ig-Superfamilies?
- calcium independent
- immunoglobulin domains
- Homophillic = 2 same vs Heterophillic = 2 diff
What are cadherins? What are the types of cadherins?
- calcium dependent
- lateral vs intercellular
E-cadherin (epithelial)
N-cadherin (neural)
P-cadherin (placental)
What are the properties affecting cell-cell adhesion strength?
- binding affinity (strength)
- spatial distribution (volume)
- activity state (phosphorylation?)
- external forces (stress)
