12-10-21 - Cell adhesion and Extracellular Matrix Flashcards
What are the 6 main cells in connective tissues?
- Fibroblasts – production of the ECM of connective tissues
- Myofibroblasts – wound healing, and specifically contraction of wound
- Blood derived (visitor cells) – mast cells, plasma cells, macrophages
- Chondroblasts – cartilage
- Osteocytes – bone
- Adipocytes – fat cells
What is the extracellular matrix?
What is it composed of?
- The extracellular matrix is an extensive molecule network outside the cell.
- It is composed of:
- Fibrillar proteins:
- Collagen – allows for strength
- Elastin – stretch
- Fibronectin and laminin – linking proteins
- All of these proteins are embedded in polysaccharides glycosaminoglycan gel (GAGs), with the GAGs linked to proteins at the appropriate places to form proteoglycans
What is the function of fibroblasts?
How are collagen fibres formed?
What does the Fibroblast also do during this process?
- Fibroblasts synthesise and secret fibrillar proteins called collagen and elastin, as well as creating proteoglycans
- In the RER, 3 propeptides are used to form a triple helix, which is known as procollagen.
- Procollagen molecules are transported to the Golgi, where they are packaged in a secretory vesicle, and sent towards the plasma membrane.
- The procollagen molecule leaves the cell via exocytosis
- The loose ends are trimmed off the procollagen to form tropocollagen
- The tropocollagen are arranged in a quarter stagger model and linked through an enzyme catalysed reaction to form a microfibril, many of which are used to form a fibril.
- Many fibrils are used to create a collagen fibre
- The fibroblast is also creating GAGs during this process
Why is procollagen secretion special in the Golgi?
How does the cell physically assemble fibrils from tropocollagen?
- Procollagen has to be packaged into specialised larger vesicles in the Golgi, as it is too big for regular vesicles.
- Fibroblasts are oriented along the tendon,
- They crawl along, and secrete a tropocollagen cable behind them using a fibropositor in order to make fibrils.
What is elastin?
Where is elastin created?
What are they made from?
How are they able to recoil?
- Elastin’s are another fibrous protein which are secreted by fibroblasts, smooth muscle cells, and chondroblast
- Elastin fibres are composed of aggregations of many elastin chains
- The elastin contains hydrophobic elements within it, so when it is stretched, it recoils in order to get these hydrophobic areas away from the aqueous environment
What are proteocoglycans made from?
What 4 things do proteoglycans contribute to extracellular matrix?
- Proteoglycans are assemblies of glycosaminoglycans and proteins, which are linked together by link proteins
- Proteoglycans provide:
- Matrix support, cushioning, and hydration
- Glue-like function
- Links between proteins of ECM
- Links between ECM and cell surface
What are GAGs?
How are they charged?
What are 2 features of them?
What are different example of GAG chains?
- Glycosaminoglycans are long chains of repeating disaccharide units
- GAGs are highly negatively charged and highly hydrated
What are integrins?
How is the extracellular to the intracellular cytoskeleton?
- Integrins are transmembrane receptors that facilitate cell to cell and cell to extracellular matrix adhesion.
- Collagen/proteoglycans can bind fibronectin (linking protein) that links to integrins
- Integrins bind to the actin cytoskeleton via adaptor proteins
What properties of other cells do myofibroblasts have?
How are myofibroblasts formed?
What are 4 ways myofibroblasts are involved in healing?
- Myofibroblasts are fibroblasts like – they can secret collagen
- Myofibroblasts have smooth muscle like properties – they can contract using smooth muscle type actin-myosin complexes.
- Fibroblasts differentiate to myofibroblasts under mechanical tension
4 Ways myofibroblasts are involved in healing:
• Myofibroblasts can proliferate and rapidly increase in number
• They secrete collagen (scaffold)
• They consolidate damaged area (fibrous scar)
• Myofibroblasts can contract, which reduces the size of the damaged area and aids in healing (think of pulling a wound closed)
What are mast cells?
Where do they come from?
What do they contain?
How do they aid in healing?
- Mast cells are progenitor cells. (Similar to stem cells)
- The originate in the bone marrow, travel to tissues, and differentiate to have granules
- These granules contain inflammatory mediators, such as histamine (anti-coagulant) and heparin (increases vascular permeability)
- When the appropriate stimulus is given, this causes the mast cell to degranulate and release the contents of its granules.
What are plasma cells?
What do they form from?
What is their function?
How can they be identified?
• Plasma cells are professional differentiated B-lymphocytes
• Their job is to make lots of anti-bodies through the secretory pathway
• Plasma cells have ER packed full of secretary component, which can be seen on photos.
The also have a large amount of cytoplasm for antibody production
What are macrophages?
What are their functions?
What do they secrete?
- Macrophages are monocytes in the tissue
- They phagocytose bacteria, secrete pro-inflammatory and antimicrobial mediators
- They also eliminate diseases and damaged cells through their programmed cell death.
What are adipocytes?
What is their structure like?
What are 4 adipocytes functions?
- Adipocytes are white fat cells
- They contain a lipid droplet, which occupies most of the cell
- This causes the organelles of the cell to be squished to the side
- Adipocytes provide insulation to the body
- Adipocytes are present in the eye to stop it from hitting bone
- Adipocytes can also act as an energy store
- Adipocytes also secretes adipokines, which send signals to regulate nutritional balance and other systems
- An example of this is the hormone leptin, which is a satiety signal.
What are mice with mutant ob genes called?
What happens to these mice?
What happened when these mice were injected with leptin?
Why was this not the same in humans?
- Mice with mutant ob genes are called obob mice.
- The white fat in these mice doesn’t produce leptin
- This results in their being no satiety signal, which causes these mice to eat excessively and become obese.
- When these mice were injected with leptin, they stopped eating ferociously and became a normal weight.
- When this was tired in humans, little change occurred.
- This was due to the fact that the white fat of obese people was still producing leptin, but they had a reduced sensitivity of leptin (leptin receptors didn’t function)
What are the functions of cell junctions/adhesion proteins?
• Cell junctions/adhesions link cells and their cytoskeleton to other cells, the extracellular matrix (ECM), and the basal lamina.
What are the 3 functions of Tight junctions?
How can epithelia be classed depending on tight junctions?
What proteins determine this?
- Tight junctions define polarity in cells – spacial difference in shape, structure and function in a cell
- This is done by fencing off membrane lipids and proteins on one side of the cell from the other by zipping together cells with tight junctions
- Tight junctions can control the passage of substances between cells (controls the paracellular pathway)
- Tight junctions can link to the actin cytoskeleton
- Epithelia can be classed as tight or leakey, depending on the ability of the tight junctions to prevent water and solute movement through the paracellular pathway.
- Claudins are the transmembrane proteins of tight junctions
- There are 24 different types of claudins, which will provide the epithelium with a different permeability
What is the function of adherens junctions?
What do they allow?
How do they achieve this?
What are some of the different cadherins in different tissues?
- Adherens junctions are anchoring junctions, which anchors actin filaments at the membrane of cells via catenin (anchor)
- Anchoring junctions allow communications of the actin network of the cytoskeleton from cell to cell (often epithelial cells)
- Adaptor proteins called vinculins link to transmembrane proteins called catenins
- Catenin then goes through the membrane, and links to the other cell via cadherins, which attach on to the other cells cadherins
What is the function of desmosomes?
How do they do this?
- Desmosomes provide a link between strong intermediate filaments in adjacent cells
- Intermediate filaments of a cell attach to plaque glycoproteins
- The plaque glycoproteins then connect to each other via desmosome specific cadherins
How are gap junctions made?
What are the 3 functions of the gap junction?
Where can gap junctions be found?
- 6 Connexin proteins make a connexon
- 3 connexons from one cell link up in pairs with 3 connexons from another cell to form a passage.
- The gap junction allows for communication between cells
- It is a hydrophilic channel that allows small molecules to pass through
- Gap junctions can also allow the coordination of function
- The heart muscle has gap junctions
What are focal adhesions?
What do they do?
What does this allow the cell to do?
What can focal adhesions also act as?
- Focal adhesions are macromolecular assemblies that act as strong spots for linking the ECM to the actin filaments of the cytoskeleton through transmembrane proteins called integrins.
- These adhesions to the ECM allow the cell to grip and crawl during migration
- Focal adhesions can also act as signalling platforms
What are hemidesmosomes?
What are they used for?
How is this different than what focal adhesions do?
Where might this be found?
- Hemidesmosomes are a junctional complex
- They link the ECM of the cell to the intermediate filaments of the cytoskeleton of the cell through transmembrane proteins called integrin
- This is more stable than focal adhesions
- It can be found linking epithelial cells to laminin the basement membrane through integrins and intermediate filaments
What is dystrophin?
What causes Duchenne’s Muscular Syndrome?
How does DMS affect mobility?
What is used to treat DMS?
- Dystrophin is an adaptor protein that links integrin to the actin/intermediate filaments of the cytoskeleton.
- Duchenne’s muscular syndrome is cause by a gene mutation, which results in the absence of dystrophin in muscle cells due to premature termination of translation.
- This premature termination is causes by a premature stop signal during translation
- DMS results in muscle weakness and wasting, which causes the patient to be unable to walk by the time they are 12.
- PTC 124 (ataluren) is a drug that overrides the premature stop signal mutation to produce regular dystrophin
Describe the first stages of cell adhesion in cancer stages
- Tumour cells accumulate, due to mutations causing a dysregulated cell cycle
- Cells have not yet breached the basement membrane
- Carcinoma in situ (carcinoma – cancer in epithelial tissue of skin/lining internal organs) (situ – in place)
Describe the stages of cancer microinvasion
- The cells begin to convert to mesenchymal cells, and the expression of cadherins is reduce, allowing cells to move more freely.
- Microinvasion begins which is aided by protrusions called invadipodia
- The secretion of metalloproteinases follows, which are enzymes that can break down proteins found in spaces between tissues, such as collagen
- The basement membrane is now breached
- In invading tumours, leading cells express integrins, which promotes interaction with the ECM and non-epithelial cells during movement
What is metastases?
Describe the progression of cancer to metastasis
- Metastases is the development of secondary malignant growths at a distance from the primary site of cancer.
- Autocrine motility factors are secreted from the tumour, which decreases the e-cadherin expression, and makes the cells more motile
- Angiogenesis factors are secreted, which promotes vascularisation to the tumour for nutrients (anti-cancer medicine called VEGFs can stop this)
- The malignant cells enter into and go through the lymphatic and blood vessels
- The cancer has now disseminated (spread), meaning it has progress to metastatic cancer
