Extracellular Matrix Flashcards
T or F: tissues are made up solely of living cells
FALSE! most of the material in our bodies is made from the ECM secreted by living cells
What things in our bodies is the ECM a large component of?
bones
cartilage
tendons
ligaments
cornea
exoskeletons in arthropods
the ‘jelly’ part of jellyfish
What does the ECM contribute to?
mass, strength, shape and form of organs
what 2 things is the ECM composed of?
proteins and polysaccharides
How do the components of the ECM assemble to make the ECM?
proteins and polysaccharides assemble into an organized meshwork
In addition to being packing material and a glue to hold cells together, what other functions does the ECM have?
it provides biochemical and mechanical signals that regulate the activities of the cell
T or F: every ECM has the same function
false! the function depends on the specific components present
what two cells are components of the outer layers of human skin (aka epithelium)?
epidermal cells
dermal cells
Describe how epidermal cells are situated to one another
they are tightly packed to one another and to an underlying ECM layer (basement membrane)
Describe the basement layer
a layer of ECM under the epidermal cells of the epithelium which they pack tightly to
T or F: epidermal cells have an extensive ECM
false - they do have ECM but not as much as dermal cells
Describe how dermal cells situate themselves to one another
they are located below the epidermis and are loosely packed with few cell-cell connections but a lot of ECM between
T or F: dermal cells have a lot of cell-cell connection and therefore not much ECM
false!! few cell-cell connections - they are loosely packed and therefore have lots of fibrous ECM between them
The dermis region consists of what type of tissue? what does this mean?
connective tissue
means there’s a lot more ECM present than cells
What do many dermal cells of dermis connective tissues have?
cell-surface receptors
What is the function of the cell-surface receptors in the dermis connective tissue?
they secrete the ECM and allow communication between the intra- and extracellular environments
List 7 components of the ECM
glycocalyx
basement membrane (basal lamina)
collagen
elastin
proteoglycans
fibronectins
integrins
Where would a glycocalyx be located?
around every cell
Describe the glycocalyx
a network of sugars made of glycoproteins and glycolipids embedded in the membrane (sugars facing outwards) that were synthesized in the ER and processed in the Golgi
What are the 2 components of the glycocalyx?
glycoproteins
glycolipids
What are the 3 functions of the glycocalyx?
gives each cell an identity that can be recognized by other cells in the body
provides some mechanical protection
mediates cell interactions (with other cells or ligands)
What is another name for the basement membrane?
basal lamina
Describe the basement membrane/basal lamina
a thin, tough, flexible continuous sheet of matrix molecules beneath every epithelial tissue
T or F: the basal lamina is a continuous layer beneath epithelial cells
true
How thick is the basal lamina?
50-200 nm
What is the main component of the basal lamina?
collagen protein
What type of organisms have basal lamina?
all multicellular animals
What type of cells is the basal lamina mostly associated with?
What other cells can the basal lamina surround?
associated with epithelial cells
but can also surround individual fat cells, muscle cells, and Schwann cells
What are the 4 functions of the basement membrane/basal lamina?
separates epithelial cells from the underlying or surrounding connective tissue
provides mechanical support for epidermal cells
creates water-tight barrier to molecular passage
provides a scaffold for regenerating cells if skin is damaged
What results from genetic defects in the basal lamina?
the epidermis detaches from the dermis which can cause severe and painful blisters
can also cause some muscular dystrophy (muscles degenerate later in life)
What are the 5 components of connective tissues?
collagen
elastin
proteoglycans
fibronectins
integrins
Describe collagen
huge protein fibres made of thousands of individual collagen molecules
Where does the assembly of collagen fibres occur?
outside the cell
How thick can collagen fibres be?
up to 100 nm
What is the main function of collagen?
to provide a structural framework for the ECM
How many different types of collagen are there throughout the body?
28
Approximately how much of all the protein in your body is collagen?
1/4
Describe the structure of collagen and how it packs together to make fibres
a triple helix (3 tightly wound chains around each other)
these triple helices are packed into repeating rows in staggered alignment
What is the function of collagen?
collagen fibre is very strong and flexible to provide the structure and strength for tissues
T or F: collagen is strong and rigid
False, it is strong and flexible
How does elastin compare to collagen?
elastin: smaller, not as strong, more resilient
Where is elastin found?
in elastic tissues like the skin and some cartilages (ex. nose, ear)
Describe the structure of elastin
smaller, less strong fibres than collagen, but very elastic and resilient
they cross-link to provide strength
What is the MAIN function of elastin? What other functions does it have?
it provides some strength but the main function is to stretch out and spring back to make tissues more elastic
How do elastins pack together?
they cross-link into very dense networks
Describe proteoglycans
small protein fibres with negative charges that are attached to long linear oligosaccharides that fill in the ECM with a porous, hydrated gel
Describe glycosaminoglycans (GAGs)
repeating sulfonated sugars that compose the oligosaccharides bound to proteoglycans
What type of oligosaccharides bind to proteoglycans?
repeating sulfonated sugars called glycosaminoglycans (GAGs)
What does GAG stand for?
glycosaminoglycan
Give 3 examples of GAGs
chondroitin sulfate
keratan sulfate
hyaluronan/hyaluronic acid
What is the function of proteoglycans? How do they achieve their function?
they form a porous hydrated gel that fills in the ECM
they can do this because they have many negative charges = good at binding water
What type of charge do proteoglycans have? why?
negative charges to bind water to make a hydrated gel to fill in the ECM
How do proteoglycans arrange themselves to make the porous hydrated gel of the ECM?
Many proteoglycans attach to a central long hyaluronic acid GAG strand to form huge aggregates
What does hyaluronic acid form?
a viscous non-compressible solution
Where is hyaluronic acid present? What is its function?
in fluid in the cavities of synovial joints to reduce friction during movement
it’s also the jelly-like vitreous humor of your eye
What do a lot of glycoproteins have? What is the purpose of this?
multiple binding sites that help the cell attach to the ECM components
Describe fibronectin
a dimeric glycoprotein that functions in many cell-ECM interactions
What is the function of fibronectin?
to assist in cell-ECM interactions
In what ways does fibronectin assist in cell-ECM interactions?
binds to cell surface receptors (with RGD sequence)
have other binding domains to bind other molecules (ex. collagen)
help determine cell shape
help determine direction of any cell migration
critical for development
What structure does fibronectin have?
dimer
2 subunits joined at the C-termini by disulfide bridges and contain similar binding domains
what sequence causes fibronectin to bind to cell surface receptors?
RGD sequence
Use an example to explain why fibronectin is critical for development
mutant mice without fibronectin die in early embryonic development
Where do the 2 subunits of fibronectin join?
at the C-termini via disulfide bridges
T or F: the binding domains on the two subunits of fibronectin are different
false, they are usually very similar
What are 2 major functions of fibronectin?
determining cell shape
directed cell migration
Describe integrins
A family of membrane receptors in animals that bind to ECM molecules
Describe the structure of integrins
heterodimers with an alpha and beta subunit
globular heads on the EC side that are curled when inactive and straight when active
What do integrins have on their EC side?
globular heads
What conformation do the globular heads of integrins have when they are inactive?
curled
What conformation do the globular heads of integrins have when they are active?
straight
What is the main function of integrins? How do they accomplish this?
they bind to the cytoskeleton on the cytoplasmic side of the membrane so they can bind to many extacellular molecules and promote ECM adhesion and communication
think: integrin = integrate ECM signals and communicate to inside of cell
What would activate an integrin?
binding of a ligand (ex. collagen)
they are membrane receptors, so they require a ligand to bind to create a conformational change
What is required to induce the straightened conformation of integrins?
binding to the cytoskeleton on the cytoplasmic side of the membrane
What does the binding of ECM fibres to integrins cause?
the activation of kinase cascades in the cytoplasm
What binds to integrins to cause kinase cascades in the cytoplasm?
ECM fibres
What can an integrin binding to an ECM molecule effect?
cell survival
growth
migration
differentiation
What is the RGD sequence?
Arginine-Glycine-Aspartate
Where are RGD sequences found?
on fibronectin, collagen, and other integrin targets
T or F: RGD is the most common sequence where integrin will bind
true
Describe how blood clotting at injury sites occurs?
platelets in blood plasma bind to the fibrinogen ECM proteins with an RGD sequence and then they bind to each other using integrins
How can blood clotting be limited?
drugs with RGD sequences can prevent the interactions between platelets in blood plasma, fibrinogen, and integrins
