Cell-matrix interactions Flashcards
Label this extracellular matrix
Label the different cells of the body;
Tell me about collagens?
What its role is?
Where it is present?
- 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
Whats the typical sequence of Collagens?
Gly-X-Y (X,Y often lysine or proline)
many prolines and lysines converted to the -OH form
What does fibrillar collagens include?
Collagens I, II and III
Are Fibrillar collagens strong ?
They are very strong and resilient to stretching
How are Fibrillar collagens packed together?
- Loose connective tissue (more random)
- Dense connective tissue (reguarly packed into sheets)
Tell me the steps to the synthesis of the pro-alpha chain
Tell me about collagen molecules half lives?
They have a long half life (10 yrs +)
Where is collagen degraded/ reformed?
At points of stress, healing, growth and cell infiltration
What are MMPs?
Where are they released?
What do they regulate?
MMPs: Matrix Metalloproteinases
Released by cells as they migrate through connective tissues
Regulate the breakdown of collagenous matrix
What is scurvy caused by?
When are defects seen?
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)
In its absence collagen trimers and fibrils are less stable. what structures see this weakness?
- Gums
- nail beds
- Poorly healing wounds and bruising
What does elastin provide?
Strength and resistance
What are elastic fibres formed from and what are they laid around?
Elastic fibres are formed from the polymer Elastin (monometic tropoelastin) and are laid around microfilaments of fibrilin
How are elastic fibres connected?
They are cross-linked to each other through similar lysine linkages as in collagen
What does elastin lack and what determines its behaviour?
Elastin lacks a defined structure but is highly hydrophobic giving random coils, hence behaviour
When does elastin synthesis occur?
What does this mean?
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
What is elastase secreted from?
Neutrophils
Elastin is not replaced after inflammation, instead what is used and what does this result in?
Instead collagen is layed down- this results in fibrosis and scarring
What do Proteoglycans provide?
Strength by water retention
they are resistant to compression (alters charge density on pressure)
Tell me about Proteoglycans protein core?
Has highly charged sugars attached, which attracts H2O and Na+ ions and forms a hydrated porous gel
Whats do hydrated gels allow?
motion of nutrients and waste products about isolated cells e.g. Chondrocytes
What does the high charge of proteoglycans provide?
give examples
Acts as a binding site for many moleucles
Example:
- Growth factors (FGFs)
- Cytokines (TGFb)
What links collagen and proteoglycans to cells?
Cell adhesion molecules which interact with cell receptors
Where is fibronectin found?
In loose connective tissue- disulphide linked dimer
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
Whats Laminin?
A cell interacting molecules which occurs in the basement membrane
What is Laminin formed from?
Its formed as a trimer of alpha, beta and gamma chains
What does laminin interact with ?
Proteoglycans
Collagen IV
cell receptors
Laminin is crucial for cell basement membrane signals, such as…?
- migration
- cell survival
- differentiation
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
What do specific integrins bind to?
Specific ECM components, especially laminins and fibronectin
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
What are Integrins needed for?
- Attachment to the matrix
- cell migration
- Wound healing
- Immune cell movement
- Metastasis
When integrins cluster at the plasma membrane, what do they form?
- Focal adhesions
- Hemidesmosomes
When do focal adhesions form?
When integrins bind to specific sequences on ECM moleucles e.g. RGD in fibronectin (laminin- more complex interaction site)
Whats the role of focal adhesions?
- anchor cells to the ECM
- cell migration
- Signal from the ECM
What do Hemidesmosomes bind?
Epithelial cells to the basement membrane
What do specific integrin bind laminin in the basement membrane to?
intermediate filaments (keratin) via plectin
Label this cell
What are cell-matrix contact sites for?
cell signalling
Label this section of a cell
These are some steps to cell signalling…
What does other signalling occur due to ?
Molecules becoming bound to the ECM and being released on ECM turnover
What does the extracellular matrix regulate events in?
- Development
- Tissue maturation
- Healing
What does the extracellular matrix help do?
- tissue strength
- resilience
- force projection
- physical boundaries
- diffusion/ filtration barriers
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
