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?
- Fibroblasts – synthesise and secrete fibrillar proteins collagen and elastin as well as proteoglycans that helps maintain the cell structural framework.
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 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 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 (mutations dysregulate cell cycle).
- Cells have not breached the basement membrane.
- Carcinoma in situ
- Cells undergo epithelial to mesenchymal transition (EMT)
Describe the stages of cancer microinvasion
- Cells convert to “mesenchymal” cells and expression of cadherins reduced
- Microinvasion starts aided by actin-based protrusions called invadipodia
- Secretion of metalloproteases (MMPs).
- Basement membrane breached.
- In invading tumours leading cells to express integrins promoting interaction with extracellular matrix and non-epithelial cells during movement.
What is metastases?
Describe the progression of cancer to metastasis
- Autocrine motility factors from tumour (increase motility of tumour cells and decrease E-cadherin).
- Angiogenesis factors (promote vascularisation; e.g., VEGFs (basis for anticancer drugs)
- Entry into and through lymphatic and blood vessels
- Dissemination – metastasis.
