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What are interactions of cells with their environment important for?
- cell migration
- axon outgrowth to targets
- cell division and survival
- differentiation
- organization into tissues
What are junctions for?
To communicate and adhere cells to one another
Are cells tightly or loosely packed in the epithelium?
Tightly packed
What happens when you scrape your skin and begin to bleed?
You remove the top layer which is the epidermis and got into the dermis which is below is that contains blood vessels which became and exposed and destroyed
What happens when a blister forms?
Your basal membrane detaches causes a space to form allowing the top layer of skin to die off while liquid enters into the space
What is glycocalyx?
An extracellular coating/ layer of carbohydrates that provides protection to the cell
What does glycocalyx surround?
It is around proteins, lipids, and molecules that bind to the cell surface
Why do cells have a net negative charge?
Partly because of the glycocalyx
What does glycocalyx mediate?
- cell-cell and cell-substratum interactions
What does glycocalyx provide for cells?
Mechanical and chemical protection
What does glycocalyx serve as for cells?
Serves as a barrier to particles moving toward the plasma membrane
What does the glycocalyx bind?
Important regulatory factors that act on the cell surface
What is the extracellular matrix?
An organized network of secreted extracellular material present beyond the immediate vicinity of the plasma membrane
What type of cells have a lot of extracellular matrix around them?
Chondrocytes
How thick is the basement membrane?
50-200nm
What does the basement membrane surround?
muscles, nerve, and fat cells
What does the basement membrane underlie?
epithelial cells of the skin, digestive & respiratory tracts, and the lining of blood vessels
What does the basement membrane provide?
Mechanical support
What does the basement membrane serve as?
Migratory substratum
What serves as a selective barrier for macromolecules (e.g. in the kidney)?
Basement membrane
What collagen type is in the basement membrane?
Collagen IV
What type of collagen is in the dermis?
Collagen I
What contains a very thick basement membrane?
The glomerulus of the kidney
What does the basement membrane of the kidney do?
It keeps proteins in the blood when it is filtered
What is kidney failure in diabetics caused by?
Thickening of the glomerular basement membrane
What are proteoglycans?
Huge protein-polysaccharide complexes (they are space filling)
What are fibronectins?
Dimers that have ECM and cell-binding domains (they are normally attached to the integrin that is on plasma membrane)
What is the shape of a laminin?
Cross shaped
Where are integrins located?
On the cell surface and are receptors for the ECM
What are collagens?
Family of fibrous glycoproteins that are only located in the extracellular space
What glycoprotein has high tensile strength that resists pulling forces?
Collagen
What is the most abundant protein in the body for humans/ animals (>25%)?
Collagen
What is collagen produced by?
Fibroblasts, smooth muscle cells, epithelial cells, bone
How many different types of collagen are there?
19 types
What are collagens restricted to?
Specific locations
Can collagens be mixed, even in the same fiber?
Yes
What is the structure of collagen?
Trimers of 3 alpha chains as a triple helix
What do collagen molecules for?
Fibrils
How are collagen fibrils formed?
By staggering parallel molecules to increase strength
What is the banding pattern caused by in collagen?
Staggering molecules with fibrils that are bundled together to form fibers
What are collagen fibrils strengthened by?
Cross-linking of lysine and hydroxylysine amino acids
What does the cross linking of collagen (lysine and hydroxylysine aa's) throughout result in?
Decreased elasticity of skin and brittleness
What does collagen provide for the extracellular matrix?
Insoluble framework
What does collagen type and arrangement determine for ECM?
Its physical properties
Why are collagen fibers in tendons parallel?
For high tensile strength
Who is collagen structured in the cornea?
In sheets where parallel fibers are perpendicular to adjacent sheets
Why is collagen structured the way it is in the cornea?
To give strength and minimize scattering of light
What is scar tissue made up from burns and injuries?
Accumulation of fibrillar collagens
What is osteogenesis imperfecta?
Mutations in type I collagen gene
What does osteogenesis imperfect cause?
Fragile bones, thin skin, and weak tendons
What are type II collagen mutations? What do they cause?
They alter cartilage and cause dwarfism and skeletal deformities
What is Ehler- Danlos syndrome?
Different collagen mutations
What does Ehler- Danlos syndrome cause?
Hyperflexible joints and highly extensible skin
What type of collagen is restricted to the basal membrane (basal lamina for humans)?
Type IV
How were collagenous proteins extracted from the basal membrane?
Using salt solutions because they are held together by non-covalent bonds such as ionic bonds
How is type IV collagen molecules arranged in basal membranes?
Lattice pattern with non-helical trimers with globular ends
What is Alport syndrome?
Inherited mutation of type IV collagen when the kidney basal lamina is disrupted
Where are there large amounts of proteoglycans?
In the extracellular matrix
What type of side chains do proteoglycans have?
Covalent GAG side chains
What are GAGs?
glycosaminoglycans - linear polysaccharies of repeating disaccharide units
Why are GAGS acidic?
Due to sulfate and carboxyl groups attached to sugar rings
How do proteoglycans form huge complexes?
By core proteins linking to hyaluronic acid (non-sulfated GAG) backbone
How do proteoglycans form hydrated gels?
By binding cations and water molecules
What are key characteristics of proteoglycans?
They fill space and resist compression
How do collagens and proteoglycan complement each other?
To give the extracellular matrix strength and resistance to deformation (similar to cartilage)
What is a modular protein?
dimer of 2 arrays of many cell and extracellular binding domains (ex: Fibronectin)
How many Fibronectin domains does each polypeptide have?
30 similar Fn domains
How many functional units are fibronectin domains arranged into?
5 or 6
What do the cell surface receptors (integrins) bind to?
RGD and other sequences in fibronectin
What is RGD?
Arg., gly., asp.,
What does RGD form?
Loop that sticks out for cell to bind via integrin receptor
How are the C-terminal ends of polpeptides linked? (fibronectin)
By disulfide bonds
Where is fibronectin localized to?
Basement membranes and connective tissue
What do fibronectin in connective tissues serve as?
Pathways for neural crest cell migration
What are the pathways that are important for embryonic development?
Fibronectin and extracellular matrix pathways
Is testing neural crest cells on a cover slip in vivo or in vitro?
In vitro
What is important to morphogenesis?
Fibronectin
What is morphogenesis?
the physical processes that give an organism its shape (what it morphes into)
What do Fn anti-bodies do to cleft formation?
Inhibits cleft formation
Where is neural crest cell migration the most extensive?
Out of neural tube
What do neural crest cells form?
All peripheral nervous system, melanocytes, and some facial bones
What are embryonic cell migrations guided by?
Extracellular molecules
What are laminins?
Family of proteins with 3 polypeptide chains that resemble a cross
How many different trimers are there for laminins?
20 different trimers
What are laminins linked by?
Disulfide bonds
What family of proteins influence cell migration, growth, and differentiation?
Laminins
What can laminins binds to?
Other laminins, cell surface receptors, proteoglycans, and other basal membrane proteins
What are the 2 cross-linked networks of basal membranes?
Collagen IV and laminin
How are collagen IV and laminins connected in basal membranes?
Entactin molecules
Are extracellular molecules static?
No
Can extracellular molecules be remodeled? When does this occur?
- Yes (degraded and reconstructed)
- Occurs during development or after tissue injury
What are matrix metalloproteinases responsible for?
Degration of extracellular molecules
1) Secreted
2) Membrane-bound forms
What diseases can occur due to excessive matrix metalloproteinases?
- arthritis
- multiple sclerosis
- atherosclerosis
- tooth decay
- cancer
What are the major extracellular membrane receptors on all cells?
Integrins
What subunits do integrins have?
Alpha and beta
How many different alpha integrin subunits are there?
18
How many different beta integrin subunits are there?
8
How many different combinations of integrin alpha and beta subunits are there?
25 different combinations
What type of cell surface receptors do most cells express? What does this allow?
Multiple integrins which allows binding to multiple ECM components
Do integrins bind to 1 or more ECM components?
More than 1