ECM Flashcards
When cells exist alone, what is the organism known as?
A unicellular organism
What two things can bacteria be and what does this mean?
Planktonic- Freely existing in bulk solution
Sessile- Attached to a surface or within a biofilm
Tell me about the need for cell adhesion and its use in bacteria?
- No permanent connections with other cells but they can adhere surfaces, food etc.
- Initial attachment may be via pili (fimbrae)
- Considered virulence factors in virulent bacteria
- Allow bacterial cells to adhere and resist immune attack
Tell me about some of the challenges faced when organisms transition from unicellular to multicellular?
Different sides of the cell have differing roles and interactions
- How to “stick” cells together
- How to have communication and transport between cells
- How to create specialised domains
What are tissues?
A tissue is an ensemble of similar cells and their extracellular matrix from the same origin that together carry out a specific function.
Whats an organ?
Organs are then formed by the functional grouping together of multiple tissues
How can cells be linked to one another?
Cells may be linked by direct interactions, or they may be held together within the extracellular matrix.
What two categories do animal tissues fall into?
- Connective tissues
Epithelial tissues
What are connective tissues and where are they found. Tell me about some characteristics
Found in bones, tendons
Properties;
- Low cell density
- abundant ECM
- Cell-cell contacts are rare
- ECM is load bearing
- Cell attachments to the ECM allowing force transmission
Tell me the properties of epithelia tissues and where it is found?
What is the extracellular matrix (ECM)?
The materials lying outside the cell are known collectively as the ECM
Whats the definition of ECM?
Any material produced by cells and secreted into the surrounding medium. usually applied to the non-cellular portion of animal tissue
What do plants and fungi produce?
What do arthropods prodice?
Plants and fungi produce an extracellular matrix or walls
Arthropods produce chitin
What are probably the most abundant biopolymers on earth?
Chitin and cellulose
Does each tissue have their own specific ECM?
yes
What does the ECM have roles in?
Normal tissue development, function and disease
What is the ECM comprised of?
The ECM is a complex network of proteins and polysaccharide chains that are manufactured by cells, secreted and modified outside the cell by several different enzymes
It can be dynamic or static
Label this ECM…
What are the three main functions of the ECM and what does this mean?
- Mechanical: Tensile and compressive strength and elasticity
- Protection: Buffering against extracellular change and retention of water
- Organisation: Control of cell behaviour by binding of growth factors and interaction with cell-surface receptors
Are the classes of macromolecules consituting the ECM in different animal tissues broadly similar?
If yes, then where do variations occur?
yes
variations in the relative amounts of these different classes of molecules and how they are organised give rise to an amazing diversity of materials.
Tell me where ECM can be found and how it is specialised to be found in this area
- Matrix of bone and teeth is highly mineralized to withstand compression
- Cornea of the eye has a transparent ECM
- The ECM of tendons is highly elastic
- Blood plasma is a liquid form of ECM
In most connective tissues, the matrix macromoleucles are secreted by cells called what?
Fibroblasts
What forms bone and cartilage?
Osteoblasts form bone
Chondroblasts form cartilage
What are the main macromolecular components of the ECM?
- Glycosaminoglycans (GAGs) - acidic polysaccharide derivatives, proteoglycans)
- Fibrous proteins – includes members of the collagen family
- Non-collagen glycoproteins - e.g., fibronectin and laminin
- Others - e.g., elastin
What are Glycosaminoglycans (GAGs)?
GAGs are unbranched polymers of repeated disaccharide derivatives, including amino sugars, sulfated acetylamino sugars and uronic acids
The equivalent glucose derivatives are also common components of GAGs.
Tell me the properties of GAGs?
- Acidic and negatively charged
- Attract positive ions (eg Na+) which attracts water causing gel formation
- Comprise 10% of ECM mass but 90% of volume; can hydrate and expand and fill up a large space
- GAGs (especially hyaluronan) provide compressive strength
- Metabolically cheap bulking agent
Whats a type of GAG and give me some of its properties?
Hyaluronan
- Hyaluronan is spun out from the cell membrane
- Enormous (107 kDa - much larger than other GAGs)
- Not sulfated
- Not attached covalently to protein – ‘stand-alone’
- Often added to the ECM to hold open areas that would otherwise fill up with cells; it is then removed by hyaluronidase after appropriate cell migration.
- Can be used to be added to ECM to keep it open for other cells to be added later
Other examples of GAGs
Give another example of a GAG, what is this?
Tell me about its assembly
Proteoglycans
- A proteoglycan is a serine-rich protein decorated with hundreds of O-linked (usually via serine), acidic, sulfated GAGs
- A specific link tetra saccharide is first assembled on a serine side chain. The rest of the GAG chain, consisting mainly of a repeating disaccharide unit, is then synthesized, with one sugar being added at a time.
Give an example of a proteoglycan?
Aggrecan
Whats an Aggrecan?
Aggrecan is a common proteoglycan in the ECM. Its core protein is decorated with around 100 chondroitin and 30 keratan chains.
Tell me about Heparan sulphate proteoglycans
Their importance
What they bind to
etc.
- Important role in cell growth.
- Bind chemokines at inflammatory sites, prolonging white-cell attracting activity.
- Bind and block certain proteases.
- Oligomerizes FGF (fibroblast growth factor), giving easier binding to its tyrosine-kinase receptor
Whats collagen and what is it comprised of?
What does it provide?
Tell bind about its structure
- Collagen is a fibrous protein consisting of the three alpha chains forming a triple helix
- Provides tensile strength to the ECM
- Hydrogen bonding between the -OH groups of HP stabilizes the triple helix
- Lysine’s can be hydroxylated and subsequently glycosylated
- Collagen chain is made up of the 3 repeating amino acids- GXY
What is scurvy?
What organisms can it occur in?
A vitamin C deficiency
It can occur in primates and guinea pigs as we rely on getting vitamin C from our diet and don’t make it
When is hydroxyproline formed and by what?
Hydroxyproline is formed post-translationally by the action of proline hydroxylase.
Tell me about how a defect in collagen underlies the bases of scurvy?
- Hydroxyproline is formed post-translationally by the action of proline hydroxylase.
- Proline hydroxylase requires vitamin C as a cofactor
- In the absence of vitamin C tissues containing collagen (gums, skin, capillaries etc.) are weakened because unhydroxylated collagen is destroyed prior to secretion
How is collagen synthesised?
- Synthesis as a pro-alpha chain on RER
- Assembly of procollagen
- Procollagen is secreted from vesicles into extracellular space
- terminal propeptides are cleaved to form 100nm long collagen chains
- hydroxylation of selected prolines and lysines
- glycosylation of selected hydroxylysines
- collagen molecules are crosslinked to form fibrils
- Oxidative deamination of hydroxylysine and lysine forms reactive aldehyde groups, which link molecules together (and also link alpha chains together too)
- collagen fibrils then self-assemble into fibres
- Collagen fibrils are highly stable and last around 10 years
What are the types of collagen and tell me about them?
- Type I – Most common fibrillar form – found in skin bones and tendons
- Type II – Similar tensile strength to cartilage
- Type IX and XII don’t form fibers and are fibril-associated.
Link type I or II fibrils.
More flexible than type I or II due to more frequent substitution of the GXY by other aas
- Type IV and VII – form a mesh structure in the basal lamina. Type IV is the key one here
Tell me about the other components of the ECM?
- Crosslinking via α helical regions.
- Hydrophobic domains are extensible due to lose random coil conformation
In which three locations is the basal lamina present?
The basal lamina- interactions between proteins
Label the primary and secondary plant cell wall
Tell me about the plant primary cell wall i.e. what each layer is comprised of?
What is collagen made up of?
Cellulose is composed of a polymer of glucose
Tell me about the structure of Hemicellulose
- Crosslink cellulose microfibrils
- Xyloglucans Xylan Galactoglucomannan Glucuronoxylan Arabinoxylan Mannan Glucomannan
- Xyloglucan can account for up to 20% of the primary wall dry weight.
- Xyloglucan has a backbone composed of 1,4-linked β-D-Glcp residues.
- Up to 75% of these residues are substituted at O6 with mono-, di-, or triglycosyl side chains
Tell me about the structure of pectic polysaccharides
What do pectin crosslinks form?
Macromolecules structures in the primary plant cell wall
Tell me about the structure of the plant secondary cell wall?
- Secondary cell walls predominantly cellulose, hemicellulose and lignin
- S1, S2 and S3 layers have different orientations of the cellulose microfibrils
- Secondary cell wall deposition results in a rigid cellular structure
Label this bacterial capsule
Label this diagram of an animal tissue
Label the types junctions between cells
What do occluding junctions do?
What are the types of occluding junctions and what organisms are they found in?
Seals gaps between epithelia cells to create an impermeable or selectively permeable barrier
types:
- tight in vertebrates
- septate in invertebrates
Tell me about adsorption of glucose from the gut?
- Specialised absorptive epithelial cells
- Express Na+ glucose symporter on the apical face
- Passive glucose carrier protein expressed on basal and lateral faces
- This only works because of the tight junctions
- The tight junctions may function to help partition the transporters as well as prevent uncontrolled fluid flow
Tell me about anchoring junctions
Transmit stresses, tethered to cytoskeletal filaments inside the cell
Tell me about the different anchoring junctions and what attachment sites they are found in?
What is an adherens junctions important for?
Important role determining shape of multicellular structures
Telll me about formation of the neural tube
Tell me about desmosome junctions?
What are they similar to?
What do they provide?
What are they found in?
- Similar to Adherens junctions but link to intermediate filaments, not actin
- Provide mechanical strength
- Found in vertebrates but absent in Drosophila
- Present in mature vertebrate epithelia
What do desmosomes form?
regions that stick cells together
The intermediate filament that desmosomes attached to is dependent on cell type. what are some of the filaments?
Keratin – most epithelia cells
Desmin – heart muscle
What do channel forming junctions do?
What are the types of this?
Create a link between cytoplasms of different cells
types:
- gap junctions (in animals)
- Plasmodesmata (in plants)
Whats the difference between gap junctions and plasmodesmata?
Plasmodesmata in plants; gap junctions in animals
Tell me about the structure of gap junctions
i.e.
What subunits are present
What do the subunits make up
types of channels
- The combination of connexons determines function and permeability
- Most cell types express more than one type of connexin
- Adjacent cells can express different connexins
- Gap-junction plaques can rapidly assemble and disassemble
Gap junction structure
Mutations in connexin genes cause several disorders. give examples of some of these disorders
- Connexin 26 – mutation leads to death of cells in the organ of Corti (electrically active sensory epithelium)
- Congential deafness
- Connexin mutations can also cause – cateracts and demyelinating disease in peripheral nerves
Tell me about signal-relating junctions?
What are some of their roles?
Allow signals to be relayed between cells across the plasma membranes at the site of cell-cell contact
Summary of different types of cell junctions
