Cell-matrix interactions Flashcards

1
Q

Label this extracellular matrix

A
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2
Q

Label the different cells of the body;

A
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3
Q

Tell me about collagens?

What its role is?

Where it is present?

A
  • most abundant protein in the body
  • major structural protein
  • exists in fibrils or is associated to fibrils or in sheets
  • most cells are within a collagenous matrix
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4
Q

Whats the typical sequence of Collagens?

A

Gly-X-Y (X,Y often lysine or proline)

many prolines and lysines converted to the -OH form

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5
Q

What does fibrillar collagens include?

A

Collagens I, II and III

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6
Q

Are Fibrillar collagens strong ?

A

They are very strong and resilient to stretching

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7
Q

How are Fibrillar collagens packed together?

A
  • Loose connective tissue (more random)
  • Dense connective tissue (reguarly packed into sheets)
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8
Q

Tell me the steps to the synthesis of the pro-alpha chain

A
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9
Q

Tell me about collagen molecules half lives?

A

They have a long half life (10 yrs +)

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10
Q

Where is collagen degraded/ reformed?

A

At points of stress, healing, growth and cell infiltration

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11
Q

What are MMPs?

Where are they released?

What do they regulate?

A

MMPs: Matrix Metalloproteinases

Released by cells as they migrate through connective tissues

Regulate the breakdown of collagenous matrix

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12
Q

What is scurvy caused by?

When are defects seen?

A

Scurvy is an Ascorbic acid deficiency

Defects are seen where there is a high turn over of collagen (cofactor for lysine and proline hydroxylase- needed for collagen crosslinks)

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13
Q

In its absence collagen trimers and fibrils are less stable. what structures see this weakness?

A
  • Gums
  • nail beds
  • Poorly healing wounds and bruising
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14
Q

What does elastin provide?

A

Strength and resistance

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15
Q

What are elastic fibres formed from and what are they laid around?

A

Elastic fibres are formed from the polymer Elastin (monometic tropoelastin) and are laid around microfilaments of fibrilin

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16
Q

How are elastic fibres connected?

A

They are cross-linked to each other through similar lysine linkages as in collagen

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17
Q

What does elastin lack and what determines its behaviour?

A

Elastin lacks a defined structure but is highly hydrophobic giving random coils, hence behaviour

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18
Q

When does elastin synthesis occur?

What does this mean?

A

Synthesis of Elastin occurs in foetus and childhood and is limited later in life

Hence wrinkling of aging skin and loss of lung function with time

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19
Q

What is elastase secreted from?

A

Neutrophils

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20
Q

Elastin is not replaced after inflammation, instead what is used and what does this result in?

A

Instead collagen is layed down- this results in fibrosis and scarring

21
Q

What do Proteoglycans provide?

A

Strength by water retention

they are resistant to compression (alters charge density on pressure)

22
Q

Tell me about Proteoglycans protein core?

A

Has highly charged sugars attached, which attracts H2O and Na+ ions and forms a hydrated porous gel

23
Q

Whats do hydrated gels allow?

A

motion of nutrients and waste products about isolated cells e.g. Chondrocytes

24
Q

What does the high charge of proteoglycans provide?

give examples

A

Acts as a binding site for many moleucles

Example:

  • Growth factors (FGFs)
  • Cytokines (TGFb)
25
Q

What links collagen and proteoglycans to cells?

A

Cell adhesion molecules which interact with cell receptors

26
Q

Where is fibronectin found?

A

In loose connective tissue- disulphide linked dimer

27
Q

Tell me about the structure of Fibronectin?

What is it secreted by?

Role?

A

Structure:6 domains which interact with different ECM molecules

Secreted from:Secreted by many cell types especially Fibroblasts

Roles:

  • Links cells to collagen matrix
  • remodelling of cytoskeleton
  • cell migration (healing and development)
  • proliferation
28
Q

Whats Laminin?

A

A cell interacting molecules which occurs in the basement membrane

29
Q

What is Laminin formed from?

A

Its formed as a trimer of alpha, beta and gamma chains

30
Q

What does laminin interact with ?

A

Proteoglycans

Collagen IV

cell receptors

31
Q

Laminin is crucial for cell basement membrane signals, such as…?

A
  • migration
  • cell survival
  • differentiation
32
Q

What type of receptors are Integrins?

How are the divided into families?

A

Integrain are heterodimeric matrix receptors (alpha beta units)

They are divided into families based upon the Beta chains

33
Q

What do specific integrins bind to?

A

Specific ECM components, especially laminins and fibronectin

34
Q

What do Integrains act as and what does this result in?

A

They act as nucleation sites for actin polymerisation

Results in stable contacts between contractile machinery and ECM

35
Q

What are Integrins needed for?

A
  • Attachment to the matrix
  • cell migration
  • Wound healing
  • Immune cell movement
  • Metastasis
36
Q
A
37
Q

When integrins cluster at the plasma membrane, what do they form?

A
  • Focal adhesions
  • Hemidesmosomes
38
Q

When do focal adhesions form?

A

When integrins bind to specific sequences on ECM moleucles e.g. RGD in fibronectin (laminin- more complex interaction site)

39
Q

Whats the role of focal adhesions?

A
  • anchor cells to the ECM
  • cell migration
  • Signal from the ECM
40
Q

What do Hemidesmosomes bind?

A

Epithelial cells to the basement membrane

41
Q

What do specific integrin bind laminin in the basement membrane to?

A

intermediate filaments (keratin) via plectin

42
Q

Label this cell

A
43
Q

What are cell-matrix contact sites for?

A

cell signalling

44
Q

Label this section of a cell

A
45
Q

These are some steps to cell signalling…

A
46
Q

What does other signalling occur due to ?

A

Molecules becoming bound to the ECM and being released on ECM turnover

47
Q

What does the extracellular matrix regulate events in?

A
  • Development
  • Tissue maturation
  • Healing
48
Q

What does the extracellular matrix help do?

A
  • tissue strength
  • resilience
  • force projection
  • physical boundaries
  • diffusion/ filtration barriers
49
Q

The extracellular matrix signal occurs via integrains (and other) receptors. What sort of processes does this signalling help to control?

A
  • differentiation
  • Epithelial polarisation
  • Cell migration pathways
  • Cell survival
  • Preventing apoptosis