ECM Flashcards
1
Q
When cells exist alone, what is the organism known as?
A
A unicellular organism
2
Q
What two things can bacteria be and what does this mean?
A
Planktonic- Freely existing in bulk solution
Sessile- Attached to a surface or within a biofilm
3
Q
Tell me about the need for cell adhesion and its use in bacteria?
A
- 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
4
Q
Tell me about some of the challenges faced when organisms transition from unicellular to multicellular?
A
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
5
Q
What are tissues?
A
A tissue is an ensemble of similar cells and their extracellular matrix from the same origin that together carry out a specific function.
6
Q
Whats an organ?
A
Organs are then formed by the functional grouping together of multiple tissues
7
Q
How can cells be linked to one another?
A
Cells may be linked by direct interactions, or they may be held together within the extracellular matrix.
8
Q
What two categories do animal tissues fall into?
A
- Connective tissues
Epithelial tissues
9
Q
What are connective tissues and where are they found. Tell me about some characteristics
A
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
10
Q
Tell me the properties of epithelia tissues and where it is found?
A
11
Q
What is the extracellular matrix (ECM)?
A
The materials lying outside the cell are known collectively as the ECM
12
Q
Whats the definition of ECM?
A
Any material produced by cells and secreted into the surrounding medium. usually applied to the non-cellular portion of animal tissue
13
Q
What do plants and fungi produce?
What do arthropods prodice?
A
Plants and fungi produce an extracellular matrix or walls
Arthropods produce chitin
14
Q
What are probably the most abundant biopolymers on earth?
A
Chitin and cellulose
15
Q
Does each tissue have their own specific ECM?
A
yes
16
Q
What does the ECM have roles in?
A
Normal tissue development, function and disease
17
Q
What is the ECM comprised of?
A
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
18
Q
Label this ECM…
A
19
Q
What are the three main functions of the ECM and what does this mean?
A
- 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
20
Q
Are the classes of macromolecules consituting the ECM in different animal tissues broadly similar?
If yes, then where do variations occur?
A
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.
21
Q
Tell me where ECM can be found and how it is specialised to be found in this area
A
- 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
22
Q
In most connective tissues, the matrix macromoleucles are secreted by cells called what?
A
Fibroblasts
23
Q
What forms bone and cartilage?
A
Osteoblasts form bone
Chondroblasts form cartilage
24
Q
What are the main macromolecular components of the ECM?
A
- 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
25
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.
26
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
27
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
28
Other examples of GAGs
29
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.
30
Give an example of a proteoglycan?
**Aggrecan**
31
Whats an Aggrecan?
Aggrecan is a common proteoglycan in the ECM. Its core protein is decorated with around 100 chondroitin and 30 keratan chains.
32
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
33
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**
34
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
35
When is **hydroxyproline** formed and by what?
Hydroxyproline is formed post-translationally by the action of proline hydroxylase.
36
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
37
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
38
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
39
Tell me about the other components of the ECM?
* Crosslinking via α helical regions.
* Hydrophobic domains are extensible due to lose random coil conformation
40
Whats the role of fibrillin in elastin deposition?
Give an example of a syndrome which can be caused by a defect in genes surrounding this?
* Elastic fibres comprise an elastin core coated with a sheath of microfibrils
* Microfibrils made of a number of glycoproteins including fibrillin.
* Microfibrils may act as a scaffold guiding subsequent elastin formation
* Defects in the **FIBRILLIN 1 gene** result in **Marfan syndrome** (weak elastic tissue)
Abraham Lincoln - long fingers, weak aorta, pigeon chest
41
In which three locations is the basal lamina present?
42
The basal lamina plays several important roles, what are these roles?
* structural
* determines cell polarity
* organises and binds cells
* forms a barrier to certain cells
* forms highways for cell migration
43
Name a GAG associated with the basal lamina?
Heparan sulphate
44
Name some proteins associated with the basal lamina?
Laminin
Type IV collagen
Nidogen (entactin)
Perlecan
45
The basal lamina- interactions between proteins
46
Tell me about the layers of the plant cell wall
There is a primary and a secondary plant cell wall
The primary is composed of: Pectin, cellulose and Hemicellulose
The secondary is composed of: cellulose, hemicellulose and lignin
47
Label the primary and secondary plant cell wall
48
Tell me the properties of the plant cell wall
* flexible allowing cell expansion and remodelling (primary)
* rigis providing strength (secondary)
* thicker, stronger, more rigid ECM in plants
49
Tell me about the plant primary cell wall i.e. what each layer is comprised of?
50
What is collagen made up of?
Cellulose is composed of a polymer of glucose
51
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
52
Tell me about the structure of pectic polysaccharides
53
What do pectin crosslinks form?
Macromolecules structures in the primary plant cell wall
54
What can methylation in pectin prevent?
crosslinking
55
Tell me about the role of **Pectin methylesterases (PMEs)?**
* Pectin methylesterases (PMEs) can demethylate pectin which is then available for crosslinking via Ca++ bridges
* More calcium available means the stiffer the cell will be. When cell is expanding it will have a low calcium level and when grown will have a high calcium level
56
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
57
Label this bacterial capsule
58
What is the bacterial capsule composed of?
High molecular weight polysaccharides
59
Some bacteria produce a biofilm, what is this?
Biofilms are densely packed communities of microbial cells that grow on living or inert surfaces and surround themselves with secreted polymers. Many bacterial species form biofilms, and their study has revealed them to be complex and diverse.
60
Tell me about the bacterial biofilm
* Matrix produced by the organism
* Hydrated extracellular polymeric substances – polysaccharides, proteins, nucleic acids, lipids
* Provide mechanical stability to the biofilm
* Mediate cohesion to surfaces and form a network that immobilises the cells
* Acts as an external digestive system – keeps extracellular enzymes in close proximity to cells
61
**summary of lecture 16**
* ECM Any material produced by cells and secreted into the surrounding medium.
* **Animals**
Glycosaminoglycans (GAGs)
Proteoglycans - proteins with GAGs covalently attached
Proteins such as collagen, elastin, fibronectin and laminin
* **Plants**
Primary cell wall - cellulose, hemicellulose, pectin and cell wall proteins
Secondary cell wall - cellulose, hemicellulose and lignin
* **Bacteria**
Capsule composed of high molecular weight polysaccharides, capsule or slime layer
62
Label this diagram of an animal tissue
63
Tell me about the epithelial layer of animal tissue and they types of connections needed and why?
* The epithelium layer delimits organs
* Need tight connections between epithelial cells to prevent leakage
* To form an organised multicellular structure cells, need to form a structure
* Cells can directly adhere to each other e.g., an epithelium or be bound by secreted extracellular materials
64
What are the two ways that cells can adhere to each other at cell junctions
* cell-cell
* cell-ECM
65
What are the three types of cell junctions?
1. **Occluding junctions**
2. **Anchoring junctions**
3. **Communicating junctions**
66
Whats an **occluding junction?**
Seal cells together into sheets (forming an impermeable barrier)
67
Whats an **anchoring junction?**
Attach cells (and their cytoskeleton) to other cells or extracellular matrix (providing mechanical support)
68
What a **communicating junction**?
Allow exchange of chemical/electrical information between cells
69
Label the types junctions between cells
70
What percentage of cell types in vertebrates are epithelial?
\>60%
71
Whats the function of junctions and epithelial?
to enclose and partition the animal body
72
Tell me the common organisation of junctions and epithelia?
* anchored to the underlying tissue via the basal lamina on one side (basal)
* Free of attachment at the other side (apical)
73
What polarity are epithelial cells
polar
74
Tell me about the characteristics and properties of epithelial cells?
* Act as selectively permeable barriers – fluid on the outside cannot
* readily permeate the epithelial membrane
* Requires occluding junctions (vertebrates – tight junctions)
75
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
76
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
77
What type of adhesions occur at anchoring junctions?
Cell-cell adhesions and cell-matrix adhesions
78
Tell me about anchoring junctions
Transmit stresses, tethered to cytoskeletal filaments inside the cell
79
Tell me about the different anchoring junctions and what attachment sites they are found in?
80
What is an **adherens** junctions important for?
Important role determining shape of multicellular structures
81
What does an adheren junction form?
What does it allow?
* Form an indirect link between actin cytoskeletons
* Allows coordination of cell activities
82
Tell me about the **Zonula adherens or adhesion belt** found at the adherens junction
* Found below the apical face of epithelial cells
* Encircles each cell in the sheet
* The actin network links via cadherins forming a linked network
* Myosin motor proteins can make this contractile and thus able to reshape
* The Adhesion Belt allows reshaping of sheets of epithelial cells
83
Telll me about formation of the neural tube
84
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
85
What do desmosomes form?
regions that stick cells together
86
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
87
Tell me about Pemphigus (Autoimmune disease)
* Antibodies against desmosomal cadherin proteins ---\> Weakened cell adhesions
* Causes leakage of body fluids into loosened epithelium (blistering of skin)
88
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)
89
What do tight junctions block?
The passage of small molecules
90
What do gap junctions do in contrast to tight junctions?
Create a passageway between cells
91
Whats the difference between gap junctions and plasmodesmata?
Plasmodesmata in plants; gap junctions in animals
92
Tell me about the functions of the gap junctions?
* In tissues with electrically excitable cells gap junctions couple cells allowing **rapid spread of action potentials**
* Important in **escape responses in fish and insects**
* Vertebrates – gap junctions in heart muscle and smooth muscle cells in the intestine **synchronises contraction**
* Provide connections between cells allowing movement and coordinated sharing of signals
* Eg. liver cells allowing a response to signals from nerve terminals that contact only some cells
93
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
94
Gap junction structure
95
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
96
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
97
Summary of different types of cell junctions
