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
What links collagen and proteoglycans to cells?
Cell adhesion molecules which interact with cell receptors
26
Where is **fibronectin** found?
In loose connective tissue- disulphide linked dimer
27
Tell me about the structure of Fibronectin? What is it secreted by? Role?
**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
Whats **Laminin?**
A cell interacting molecules which occurs in the basement membrane
29
What is Laminin formed from?
Its formed as a trimer of alpha, beta and gamma chains
30
What does laminin interact with ?
Proteoglycans Collagen IV cell receptors
31
Laminin is crucial for cell basement membrane signals, such as...?
* migration * cell survival * differentiation
32
What type of receptors are **Integrins**? How are the divided into families?
Integrain are **heterodimeric matrix receptors** (alpha beta units) They are divided into families based upon the **Beta chains**
33
What do specific integrins bind to?
Specific ECM components, especially laminins and fibronectin
34
What do Integrains act as and what does this result in?
They act as nucleation sites for actin polymerisation Results in stable contacts between contractile machinery and ECM
35
What are Integrins needed for?
* Attachment to the matrix * cell migration * Wound healing * Immune cell movement * Metastasis
36
37
When integrins cluster at the plasma membrane, what do they form?
* Focal adhesions * Hemidesmosomes
38
When do focal adhesions form?
When integrins bind to specific sequences on ECM moleucles e.g. RGD in fibronectin (laminin- more complex interaction site)
39
Whats the role of focal adhesions?
* anchor cells to the ECM * cell migration * Signal from the ECM
40
What do **Hemidesmosomes** bind?
Epithelial cells to the basement membrane
41
What do specific integrin bind laminin in the basement membrane to?
intermediate filaments (keratin) via plectin
42
Label this cell
43
What are cell-matrix contact sites for?
cell signalling
44
Label this section of a cell
45
These are some steps to cell signalling...
46
What does other signalling occur due to ?
Molecules becoming bound to the ECM and being released on ECM turnover
47
What does the extracellular matrix regulate events in?
* Development * Tissue maturation * Healing
48
What does the extracellular matrix help do?
* tissue strength * resilience * force projection * physical boundaries * diffusion/ filtration barriers
49
The extracellular matrix signal occurs via integrains (and other) receptors. What sort of processes does this signalling help to control?
* differentiation * Epithelial polarisation * Cell migration pathways * Cell survival * Preventing apoptosis