Extracellular Matrix (ECM) Flashcards
What is the ECM?
ECM is a 3D network of proteins and molecules surrounding and supporting the cells and tissues.
Created by cells.
Is the ECM small and mat-like in the connective tissue or the epithelial tissue?
Epithelial tissue
What is the structure of the ECM in the tendon for high tensile strength?
rope-like
Two reasons why ECM is important?
- structural
- cell behaviour (cues given from ECM substrate to cells)
Which cell type secretes the ECM in connective tissues?
fibroblasts
Which type of fibroblasts form cartilage?
chondroblasts
Which type of fibroblast forms bone?
osteoblasts
What are the three major classes of ECMs?
- proteoglycans and glycosaminoglycans (GAGs)
- fibrous proteins
- glycoproteins
Which ECM class are these proteins found in?
- hyaluronan
- perlecan
- decorin
- aggrecan
proteoglycans and glycosaminoglycans (GAG)
Which ECM class are these proteins found in?
- type IV collagen
- fibrillar collagen
fibrous proteins
Which is the largest class of ECM proteins?
glycoproteins
Which ECM class are these proteins found in?
- laminin
- nidogen
- fibronectin
glycoproteins
How many ECM proteins do mammals have?
300
What are the two types of ECM assemblies distinguished between tissues?
- Basal lamina (basement membrane)
- Connective tissue
Where do you find basal laminae?
it underlies all epithelial and surrounds some non-epithelial cell types incl.
- multinucleated muscle fibre in skeletal muscle
- entire length of myelin sheath
What is the primary function of the basal membrane?
Provide mechanical stability
What are some other functions the basement membrane may have?
Selective filter
Determines cell polarity
Can influence cell behaviour
Highway for cell migrations
What is carcinoma?
cancer of the epithelial cell
How do cancer cells eat through the basement membrane?
Express matrix metalloproteases - enzymes capable of degrading ECM proteins
What are the interwoven networks of the basal laminae?
- Laminin network
- Perlecan network
- Type IV collagen
Which mesh-works does nidogen bind to in basement membrane?
Laminin
Type IV collagen
How do cells interact with type IV collagen and laminin on basement membrane?
via intern heterodimers
What are the primary organisers of the basal lamina sheet?
Laminin
What are the three subunits of laminin? What shape do they make?
alpha chain
beta chain
gamma chain
crucifix shape
How many genes encode for laminin?
11
Basal epithelial cells are attached to basement membrane. What attaches them?
Hemidesmosomes
What are hemidesmosomes?
Cell-matrix junctions that help anchor the epithelial cells to the basement membrane
What diseases can mutations in hemidesmosome proteins lead to?
severe skin blistering diseases
What family of proteins does collagen belong to?
fibrous proteins
Which tissue type secretes collagen in large quantities?
connective tissue
How many chains of alpha polypeptide are there in collagen?
3 in left handed helix
What is the triplet series in collagen’s alpha chain?
glycine - x - y
x usually is proline
y usually is hydroxyl proline
How many genes code for collagen alpha chains?
42
Which types of collagens do we find in connective tissue/ECM?
fibril forming collagen
fibril-associated collagen
Which collagen is an essential part of hemidesmosomes?
transmembrane collagen
Which type of collagen is found in basal laminae?
network-forming collagen
Which type of collagen forms a network/sheet?
type IV collagen
What is the difference between fibril forming collagen vs type IV collagen?
fibril forming collagen is more rigid and elongated
What is the function of the neuromuscular junction (NMJ)?
The NMJ relays signals between the axon terminal of a motor neuron and a skeletal muscle fiber, allowing muscle contraction
What happens to the motor nerve cells when a skeletal muscle injury cuts a nerve?
The motor nerve cells connected to the muscle fiber degenerate.
Why is the basal lamina around the neuromuscular junction able to direct nerve regeneration?
Unique composition of basement membrane different to that of the surrounding muscle
Guides nerve (but not muscle) regeneration
What do motor neurone axons deposit at at NMJ?
the neurotransmitter acetylcholine (ACh).
What do muscle cells deposit at the NMJ?
laminin
What is the main component of ground substance?
glycosaminoglycans (GAG)
Which cell secretes and remodels the ECM in connective tissue?
fibroblast
Are the long unbranched polysaccharide chains negative or positively charged?
highly negatively due to sulphates and carboxyl groups on sugars
Are GAGs hydrophilic or hydrophobic?
hydrophilic
What are the four types of GAGs?
- Hyaluronic acid
- Chondroitin sulphate
- Heparin sulphate
- Keratan sulphate
What is created when GAGs bind to a core protein?
proteoglycan
Which GAG does not form a proteoglycan?
hyaluronic acid
Where and what synthesises hyaluronic acid?
Hyaluronan synthase enzyme
On the plasma membrane
Where are the GAGs bound to core proteins?
Golgi apparatus
What is added to a serine on the core protein?
tetrasaccharide
What makes up the proteoglycan Aggrecan?
Chondroitin sulfate
Keratan sulfate
Core protein
Are decorin and perlecan GAGs or proteoglycans?
proteoglycans
Which protein type can act as reservoirs due to their binding of signalling molecules?
proteoglycans
Which GAG forms a hydrogel?
hyaluronic acid
What does hyaluronic acid molecules attract (due to their negative charge)?
Hint: not water
A cloud of positively charged sodium ions
What does the cloud of positively charged sodium ions surrounding hyaluronic acid attract?
Water
What is a medical application of hyaluronic acid?
Inject hyaluronic acid into knee joint of those with cartilage damage.
Hydrogel forms in knee and eases symptoms from grinding.
Organisation of collagen fibrils. Fill in gaps:
Precursor alpha chain
Proollagen triple helix (loose ends)
Collagen molecule
?
Collagen fibre
Collagen fibril
How do the three alpha chains assemble into a procollagen?
via pro collagen peptidase
Lysyl oxidase (LOX) deaminates lysine and hydorxylysine residues on collagen.
Causes reactive aldehyde groups.
What type of links are formed from this?
covalent links
Which are larger and stronger, collagen fibrils or collagen fibres?
collagen fibres
Which type of collagen helps form fibres from fibrils?
Fibril-associated collagens
What is a main function of collagen fibrils/fibers?
Resistance against tensile stress (stretch)
How does scurvy come about?
Vitamin C deficiency
Less hydroxyproline
Collagen triple helix cannot form
What coils does elastin protein consist of?
alternating hydrophobic (random coils) and hydrophilic (alpha helical) domains
Which tissues is elastin prominent in?
Ones that need to be elastic.
E.g., artery
Dermis
