Extracellular matrix

Question 1

cells must cohere if they are to form an organized multicellular structure that can withstand and respond to the various external forces, what are the 2 main ways by which cells are held together?

Answer 1

1. Direct interactions by cell-cell junctions
2. within the extracellular matrix by cell-matrix junction

Question 2

What is extracellular matrix (ECM)?

Answer 2

• a network of proteins and polysaccharide chains secreted by cells
• cell-matrix junction link cytoskeleton of cells to ECM, allowing cells to move through matrix and monitor changes in its mechanical properties
• ECM and the cells distributed sparsely within it form the connective tissues

Question 3

What is the main stress bearing component in connective tissues?

Answer 3

• ECM
• tensile strength comes from collagen

Question 4

What is the main stress bearing component in epthelial tissue?

Answer 4

The cytoskeleton of the cells that is anchored to cell-cell junction, connecting cells together

Question 5

How is the epithelial tissue linked to the basal lamina?

Answer 5

cytoskeleton of epithelial cells is linked to basal lamina via cell-matrix junction

Question 6

What is basal lamina

Answer 6

• thin mat under epethelial tissue
• specialised extracellular matrix of epithelial tissue
• consists mainly of laminins, type IV collagen, entactin, perlecan
• mechanical strength
• perlecan crosslinks the elements of basal lamina

Question 7

What are the main types of cell junctions?

Answer 7

• tight junctions

cell-cell anchoring junctions:

• adherens junctions
• desmosome

chanel-forming junctions:

• gap junction

cell-matrix anchoring junctions:

• hemidesmome
• actin-linked cell-matrix junction

Question 8

What is the function of tight junctions?

Answer 8

• holds cell together near appex
• seal gap between cells
• prevent leakage of molecules

Question 9

Describe tight junctions

Answer 9

• branching network of sealing strands
• each seal strand a long row of transmembrane adhesion proteins (mainly claudins)

Question 10

What is the function of gap junctions?

Answer 10

• create channels between cells
• allow small water soluble molecules and ions to pass through

Question 11

describe gap junctions

Answer 11

• consist of channel-forming proteins connexins
• 6 connexins assemble to form 1 connexon
• two connexons of adjacent cells align to form aqueous channel
• gap junction has many pairs of connexons in paralell, forming sieve
• conformational change depend on [Ca²⁺​]: low [Ca²⁺​] open, high [Ca²⁺​] close

Question 12

What is the function of adherens junction?

Answer 12

• joins actin bundle in one cell to that of the next cell
• tissue remodelling

Question 13

How does adherin junction link actin filaments of cells together?

Answer 13

cytoplasmic cadherin tail binds to p120-catenin and β-catenin, β-catenin binds to α-catenin, α-catenin recruits actin-binding proteins

Question 14

Adheren junctions often occur in the form of adhesion belts in epithelial tissues, describe adhesion belts.

Answer 14

• a belt of actin and myosin filament ring on inner surface of cells
• contractionof actin and mysosin bundles allow for constriction in adhesion belts
• important for folding of epithelial tissue into tubes

Question 15

What is the function of desmosome?

Answer 15

• Joins intermediate filaments in one cell to that of the next cell
• provide mechanical strength

Question 16

How does desmosomes link intermediate filaments of cells together?

Answer 16

cadherins link to intermediate filaments through adaptor proteins such as plakoglobins and desmoplakin

Question 17

what is the function of hemidesmosome?

Answer 17

anchors intermediate filaments of cell to the basal lamina

Question 18

How does hemidesmosomes link intermediate filament of cells to ECM?

Answer 18

• via transmembrane glycoprotein integrin
• integrin binds to adaptor protein plague, which binds to intermediate filaments

Question 19

what is the function of actin-linked cell-matrix junction?

Answer 19

anchors actin bundle of cell to basal lamina

Question 20

What are the main transmembrane adhesion proteins?

Answer 20

two main superfamilies: cadherin (cell-cell) and intergrin (cell-matrix)

Question 21

What are the models of cell-cell adhesion?

Answer 21

• homotopic: interaction within same plasma membrane surface
• homophillic: interaction of the same type of adhesion molecules between different cells
• heterophillic: interaction of different adhesion proteins between different cells

Question 22

Describe cadherin

Answer 22

• interaction between cadherins is Ca²⁺ dependent: high [Ca²⁺] –> rigid, strong interactions
• weak individual interactions, strong collective strength –> avidity
• binds to adaptive proteins by their intracellular domain

Question 23

Describe integrin

Answer 23

• alpha and beta subunits
• binds to collagen of ECM and cytoskeleton of cells
• mutliple interaction interfaces –> avidity
• cell signalling:
  
  • takes signal outside cell, relay signal inside cell
  • takes signal inside cell, relay signal outside cell
  • signals by conformational changes: in active state, cytoplasmic tails of alpha and beta subunits are brought apart, allowing the extracellular domain to extend

Question 24

describe collagen

Answer 24

• secreted by fibroblast
• triple stranded helical structure
• rich in glycine (flexibility) and proline (specificity)
• extremely strong

Question 25

How is collagen organised in the skin?

Answer 25

• alternating orientation like plywood –> tensile strength

Question 26

what connects intergrin to collagen?

Answer 26

fibronectin

Question 27

what is the role of proteoglycans in the ECM

Answer 27

• space fillers
• attached to single core protein chain
• have negatively charged polysaccharides: glycosamine glycans
• lots of anions amino acids, attract water and cause swelling, resist compression