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Medicine week 5 > Extracellular Matrix > Flashcards

Extracellular Matrix Flashcards

1
Q

Define Extracellular matrix

A

non-cellular component present in all tissues and organs

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2
Q

Define the two types of extracellular matrix

A
  1. Interstitial connective tissue matrix - Surrounds cells and provides structural scaffolding for tissues
  2. Basement - Separates the epithelium from the surrounding Stroma
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3
Q

State the components that make up the ECM

A

A complex network or proteins and polysaccharides that are secreted locally by cells and remain closely associated with them

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4
Q

State the function of the ECM

A

-Provides mechanical and structural support
-Tensile strength
-Determines cellular microenvironment
Anchors cells (through cell-ECM junctions)
Strongly influences embryonic development
Provides pathways for cellular migration (eg wound repair)
Sequesters growth factors
Provides a residence for roaming phagocytic cell
Establishes and maintains stem cell niches

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5
Q

Describe the acellular components of supporting/connective tissue

A

Fibres - Collagen and elastin

Ground substance - proteoglycans, glycosaminoglycans, glycoproteins

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6
Q

State the 5 classes of macromolecules of the acellular component of tissue

A
  • Collagens
  • Elastin
  • Proteoglycans
  • Hyaluronan (a glycosaminoglycan)
  • other glycoproteins
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7
Q

Define collagen

A

Major insoluble fibrous protein in the ECM

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8
Q

State the structural features of collagen

A

3 collagen polypeptides form a triple helix.

The collagen polypeptides consist of a Gly-X-Y repeat motif

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9
Q

State the two main classifications of collagen and their function

A

Fibrillar confers strength

Sheet/network forming supports and filters

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10
Q

Give examples of different types of collagen and their location

A

Class I - Dermis, tendons, ligaments, bones, fibrocartilage
Class II - Hyalin cartilage (articular cartilage)
Class III - Liver, bone marrow, lymphoid organs, also in granulation tissue
Class IV - Basement membrane
Class V - linker to basement membrane

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11
Q

Define elastin

A

Structural protein that is arranged as fibres

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12
Q

State what is required for the assembly of functional fibres in elastin

A

It requires the presence of a structural glycoprotein known as - Fibrillin

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13
Q

Describe the composition and arrangement of the ECM in different tissue

A

Loose, irregular connective tissue - lymphoid tissue
Dense, irregular connective tissue - Dermis
Dense, regular - ligaments and tendons
Bone
Cartilage

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14
Q

Define ground substance

A

amorphous, gel-like, non fibrous substance surrounding cells and fibres

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15
Q

State what ground substance is composed of

A

consists of large molecules called glycosaminoglycans (GAGs or mucopolysaccharides) which will link together with a core protein to form larger molecules called proteoglycans (mucoproteins)

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16
Q

State the function of the ground substance

A

It is very good at absorbing water due to its polar nature and so is resistant to compressive forces

17
Q

Give examples of different GAGs and their location

A

Hyaluronic acid (hyaluronen) - synovial fluid
Chondroitin sulphate - cartilage
Keratan sulphate - cartilage
Heparan sulphate - basement membrane

18
Q

State the features of GAGs

A

They are extremely hydrophilic
They adopt extended conformations to become a water swollen 3D network
Enables matrices to stand high compressive force

19
Q

Give examples of different proteoglycans, their location and their associated GAGs

A

Aggrecan - location - cartilage - GAGs - Chondroitin sulphate and keratan sulphate

Perlecan - location - basement membrane - GAGs - Heparan sulphate

Syndecan - location - cartilage - GAGs -chondroitin sulphate and heparan sulphate

Decorin - location - widespread in connective tissue - GAGs - chondroitin sulphate and dermatan sulphate

20
Q

How are aggregates formed

A

aggrecan proteoglycans assemble along a hyaluronic acid core to form a negatively charged aggregate with hydrating properties in cartilage.

21
Q

Describe how aggregates behave in cartilage

A

It interacts with type II collagen and together they resist tensile force and provide resistance to deformation

22
Q

Give examples of other glycoproteins and their function

A

Fibrillin - controls deposition and orientation of elastin
Fibronectin - Linker role in the basement membrane, organises the ECM and participates in cell attachment to BM
Laminin - Primary organiser of basement membrane layer

23
Q

Describe the role of laminin at the dermal-epidermal junction

A

Integrin in the hemidesmosomes bind to laminin in the BM which maintains integrity in the dermo-epidermal junction

24
Q

State the component that synthesises ECM components

A

fibroblasts

25
Q

State what the fibres of the ECM are synthesised as and their post-translational modifications as well as their assembly

A

Collagen is synthesised as pro-collagen. Its translational modifications include glycosylation and hydroxylation. It is assembled as a triple helix

Elastin is synthesised as tropoelastin. It translational modification is hydroxylation. It is assembled as a fibrillin scaffold with cross linked fibres

26
Q

Describe how proteoglycans are synthesised in the ECM

A
  • The core protein is synthesised by the rough endoplasmic reticulum.
  • The addition of a polysaccharide attached as a disaccharide repeats in the Golgi
  • It is delivered to the extracellular compartment by exocytosis
  • It is assembled with other ECM components
27
Q

State the stages of ECM remodelling

A

deposition - modification - degradation

28
Q

Give examples of the deregulation of ECM remodelling

A

Hyperproliferation of fibroblasts and excess ECM can lead to fibrosis

The destruction of the ECM by collagenase can lead to invasion of a host by bacteria

Destruction of the basement membrane by Matrix-metalloproteinases can lead to tumour cell invasion

29
Q

State the composition of the basement membrane

A

Collagen IV
Laminin
Nidogen
Perlecan

30
Q

State where the basement membrane is found

A

underneath endothelia and epithelia

around myocytes, neurones and adipocytes

31
Q

State the functions of the basement membrane

A 
Support 
Binding to underlying connective tissue 
Mediates signals between cells and connective tissue 
Determines cell polarity 
Permits flow of nutrients 
Path for cell migration 
Barrier to downward growth
32
Q

Give examples of disorders of the basement membrane

A

Cancer - Epithelial tumours are regarded as malignant when they breach the basement membrane

Diabetes mellitus - thickening of the basement membrane in glomerulus in the kidney changes permeability

Epidermolysis bullosa - affects attachment of epidermis to the basement membrane

Goodpastures syndrome - Autoantibodies to collagen IV will destroy the basement membrane in the glomerulus and lung

33
Q

Describe the components of bone

A

Acellular
30% organic
-Collagen I
-Osteocalcin

70% inorganic
-hydroxyapatite

Cellular
Osteoblasts - synthesise osteoid
Osteoclasts - Degrade osteoid
Osteocytes - Maintenance and communication

The osteoid is the ECM of bone and is synthesised by osteoblasts

34
Q

Describe the structure of cartilage

A

Consists of a dense network of collagen II and elastic fibres embedded in chondroitin sulphate.
The cells of mature cartilage called chondrocytes synthesise cartilage. A membrane of dense irregular connective tissue called the perichondrium covers the surface of most cartilage. It is also avascular appart from in the perichondrium.

35
Q

Describe the different types of cartilage

A

Hyalin cartilage - Few visible collagen fibres, avascular , has perichondrium except for articular cartilage

Fibrocartilage - abundant collagen fibres, avascular, chondrocytes aligned, no perichondrium

Elastic cartilage - Contains elastic fibres, avascular, has perichondrium

36
Q

Describe conditions where the ECM goes wrong

A

Elastin - Supravalvular Aortic Stenosis (SVAS) - arterial defects

Fibrillin-1 - Marfan syndrome: skeletal, ocular and cardiovascular abnormalities

Collagen - Ehler Danlos syndrome - Joint and skin abnormalities

Karaten sulphate - Macular corneal dystrophy: corneal transparency

perlecan - Silverman-Handmaker type of dyssegmental dysplasia (DDSH): Neonatal lethal dwarfism

Medicine week 5 (2 decks)

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