WEEK 7 (Extracellular Matrix) Flashcards
What is the earliest life on earth thought to have originated from?
Simple, single-celled organisms
[atmospheric oxygen is credited for the sudden burst of evolutionary diversity]
Why is predation thought to have played a key role in the evolution of multicellularity?
Larger multicellular organisms would be able to engulf and ingest their smaller, single-celled neighbours
What did the genome sequencing of choanoflagellate reveal?
Numerous molecules involved in cell adhesion, signalling and the formation of the extracellular matrix were all present prior to the rise of the metazoan lineage (earliest multicellular animal life)
What is each multicellular organism built from?
Organised collections of cells
What is the Extracellular Matrix (ECM)?
The non-cellular component present within all tissues and organs and provides physical scaffolding for the cell structures and initiates crucial biochemical and biomechanics cues that are required for tissue morphogenesis, differentiation and homeostasis
What are the functions of the Extracellular Matrix (ECM)?
- Helps cells to bind together
- Regulated a number of cellular functions (e.g adhesion, migration, proliferation and differentiation)
- Provides support and anchorage for cells
- Provides mechanical support for tissues and organ architecture
- Place for active exchange of different metabolites
What is the Extracellular Matrix (ECM) formed by?
Macromolecules locally secreted by resident cells
What is the Extracellular Matrix (ECM) formed by?
Macromolecules locally secreted by resident cells
What extracellular structures do cells synthesise and secrete?
- Cell walls of plants
- Extracellular matrix (ECM) of animal cells
- Intercellular junctions
What is the cell wall?
An extracellular structure that distinguishes plant cells from animal cells
Which organisms have cell walls?
- Plants
- Prokaryotes
- Fungi
- Protists
What are the functions of the cell wall?
- Protects the plant cell
- Maintains its shape
- Prevents excessive uptake of water
What are plant cell walls composed of?
Cellulose fibers embedded in other polysaccharides and protein
What is the Extracellular Matrix (ECM) in animal cells composed of?
- STRUCTURAL PROTEINS = Collagen, Elastin & Fibrillin
- PROTEOGLYCANS
- SPECIALISED PROTEINS = Fibronectin & Laminin
What are the properties of the Extracellular Matrix (ECM) in animal cells?
- Animal cells lack cell walls but are covered by an EXTRACELLULAR MATRIX (ECM)
- ECM proteins bind to receptor proteins in the plasma membrane called INTEGRINS
Define Extracellular Matrix (ECM)
A network of interstitial proteins that constitutes a significant proportion of any tissue
What are the two basic structural forms of ECM?
- Interstitial Matrix
- Basement Membrane
What are the properties of the Interstitial Matrix?
- Present in the spaces between cells in CONNECTIVE TISSUE and between the PARENCHYMAL EPITHELIUM and underlying VASCULAR and SMOOTH MUSCLE structures
- Synthesised by MESENCHYMAL CELLS
- Forms a THREE DIMENSIONAL AMORPHOUS GEL STRUCTURE
What are the main components of the Interstitial Matrix?
- Fibrillar & Non-fibrillar collagen
- Fibronectin
- Elastin
- Proteoglycan
- Hyaluronate
What are the properties of the Basement Membrane?
- Interstitial fluid becomes highly organised around epithelial cells, endothelial cells & smooth muscle cells forming the SPECIALISED BASEMENT MEMBRANE
- Synthesised by underlying MESENCHYME and overlying EPITHELIUM
What are the functions of Basement membranes?
- Separate different tissues
- Provide mechanical support
- Barrier to macromolecule and cellular movement
- Substrate for cell migration
- Generate signals that maintain cell survival
What do each of the proteins of the extracellular matrix contain?
Binding sites for one another and for receptors on the cell surface -> Various extracellular materials interact to form an interconnected network that is bound to the cell surface
What is Collagen?
A family of fibrous glycoproteins that are present only in the extracellular matrix
What are the properties of Collagen?
- High tensile strength & Resistance to pulling forces
- Produced primarily by fibroblasts
- 28 types of human collagen
What do all collagen share in common?
- All TRIMERS consisting of three polypeptide chains called ALPHA CHAINS
- Three polypeptide chains are wound around each other and arranged into bundles
[triple stranded collagen -> fibrils -> fibers]
What are the properties of Fibronectin?
- Consists of a linear array of distinct domains giving each polypeptide a modular construction
- Each fibronectin polypeptide is constructed from a sequence of around 30 domains
- Around 30 fibronectin domains combine to form fiver or six larger functional units
What do each of the two polypeptide chains that make up a fibronectin molecule contain?
- Binding sites for numerous components of the ECM
[facilitate interactions that link these diverse molecules into a stable, interconnected network] - Binding sites for receptors on the cell surface
[Hold the ECM in a stable attachment to the cell]
What does a proteoglycan consist of?
A core protein molecule to which chains of glycosaminoglycans (GAGs) are covalently attached
Describe the structure of Proteoglycans
- Repeating disaccharide chains (Amino sugar & Uronic acid)
- Highly acidic due to the presence of both sulfate and carboxyl groups attached to the sugar rings
How can proteoglycans of the extracellular matrix be assembled into gigantic complexes?
By linkage of their core proteins to a molecule of hyaluronic acid (a non-sulfated GAG)
What are the functions of Proteoglycans?
- Form a porous, hydrated gel that fills the extracellular space and resists compression forces
- Cell signalling since growth factors bind to proteoglycans
What does the ECM acting as a ‘sink’ for growth factors and other signalling molecules allow?
The formation of a stable signalling gradient
Describe the importance of fibronectin and other extracellular proteins are evident during embryonic development
Development is characterised by waves of cell MIGRATION during which different cells follow different routes from one part of the embryo to another -> MIGRATING CELLS are guided by proteins (e.g fibronectin) -> Proteins are contained within the molecular landscape through which they pass
What are Laminins?
A family of extracellular glycoproteins that consist of three different polypeptide chains linked by disulphide bonds and organised into a molecule resembling a cross with three short arms and one long arm
What are the properties of Laminins?
- 15 types
- Greatly influence a cell’s potential for migration, growth and differentiation
- Bind tightly to cell-surface receptors
- Bind to other laminin molecules, to proteoglycans and other components of basement membranes
What are the four major types of tissues in animals?
- Connective
- Epithelial
- Nervous
- Muscle
What distinguishes connective tissue greatly from the other tissues?
In connective tissues, extracellular matrix is plentiful and carries the mechanical load
What do burns or traumatic injuries to internal organs lead to?
An accumulation of scar tissue which consists largely of fibrillar collagen
What does Fibrosis result from and where does it most often occur?
Fibrosis results from excessive production of collagen-containing connective tissue
Fibrosis most often occurs in the lungs (PULMONARY FIBROSIS) and liver (CIRRHOSIS) where the collagen-containing scar tissue gradually replaces the normal tissue of the organ
What are the symptoms of Pulmonary Fibrosis?
- Stiff lungs
- Low blood oxygen
- Crackles lung sounds
What do mutations in genes encoding type II collagen alter?
The properties of cartilage tissue causing dwarfism and skeletal deformities
Describe Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels and other organs and tissues
CAUSE: Mutations in genes that code for the synthesis of enzymes that convert pro-collagen to mature collagen. Mutations disrupt the production or processing of collagen, preventing these molecules from being assembled properly.
SYMPTOMS:
- Joint hypermobility
- Stretchy skin
- Fragile skin that breaks or bruises easily
Describe Osteogenesis Imperfecta
Osteogenesis Imperfecta is a group of genetic disorders that mainly affect the bones
CAUSE: Mutations in genes encoding type I collagen
SYMPTOMS:
- Bones that fracture easily, often from mild trauma with no apparent cause
- Scoliosis
- Blue Sclerae
What is distinguishable about type IV collagen?
- Non-fibrillar and is restricted to basement membranes
- Organised into a network that provides mechanical support & serves as a lattice for the deposition of other extracellular materials
- Non-helical segments interspersed along the molecule & globular domains at each end
[NON-HELICAL SEGMENTS = make molecule flexible GLOBULAR ENDS = sites of interaction between molecules that give the complex its lattice-like character]
Describe Alport syndrome
Alport syndrome is an inherited kidney disease in which the glomerular basement membrane is disrupted
CAUSES: Mutations in type IV collagen genes
SYMPTOMS:
- Proteinuria (Protein in pee)
- Hematuria (Blood in pee)
- Hypertension
- Hearing loss
- Vision loss
SYMPTOMS AS KIDNEY DECLINES
- Swelling
- Fatigue
- Nausea and vomiting
- Muscle cramps
Describe Marfan syndrome
An autosomal dominant genetic disorder of the connective tissue caused by a mutation in FBN1 gene on chromosome 15 that determines structure of FIBRILLIN -> Fibrillin is a protein important in connective tissue & Elastic fibers
AFFECTS:
- bones
- joints
- eyes
- blood vessels
- heart
SYMPTOMS:
- Unusually long limbs or long toes
- Cardiovascular problems
DIAGNOSIS:
- Detected during childhood
- Multiple doctors (at least 3) are needed to look for symptoms for the person to be given treatment
TREATMENT:
- Beta blockers (for heart symptoms)
- Propranolol (prevent aortic aneurysms)
- No cure
What is a cell junction?
A type of structure that exist within the tissue of some multicellular organisms or a complex structure if protein that exist between cells or between cells and matrix
What are the functions of cell junctions?
- Connect cell to other cells
- Hold the cell together
- Functions as a barrier
- Helps to maintain the polarity
What are the three types of cell junctions in animal cells?
- Tight junctions
- Desmosomes
- Gap junctions
What is the function of Tight junctions?
Membranes of neighbouring cells are pressed together, preventing leakage of extracellular fluid
What is the function of Desmosomes/Hemidesmosomes?
Fasten cells together in strong sheets
What is the function of Gap junctions?
Communicating junctions that provide cytoplasmic channels between adjacent cells
