Tuesday, March 10, 2009
- This week we’re going to discuss the extracellular matrix & how cells
can crawl on that extracellular matrix to drive cell mobility.
- Last week we learned about cell junctions in b/w epithelial cells. We
saw that there were 3 different types, that there were anchoring junctions
that connect the cells together, that there are sealing junctions, occluding
junctions, called tight junctions which seal the gap in b/w these cells &
also that there are gap junctions which allow for communication b/w
these cells. All of these junctions are found on the lateral side of an
epithelial cell. We learned how the apical side of that cell will face the
lumen of an organ or the outside of the body.
- This week we’re going to be discussing what is going on at the base of
these cells – what is this connective tissue below the cells that these cells
are sitting on?
- Here is a cartoon of what it looks like right here – what we’re looking at
is this would be the basal plasma membrane right here so the base of the
cell & here in green, these are receptors from the cell that are reaching
out through that plasma membrane, transmembrane proteins, so that’s
why they’re poking out through these holes here. These receptors reach
out & contact this matrix of different types of proteins & this is what is
called the extracellular matrix.
- So we’ve learned that cells interact with each other & today we’ll talk
about how they also interact with non-cellular extracellular material.
- Diagram: This is the extracellular matrix. This is a protein & sugar
network in the extracellular space.
- Diagram: This is a fibroblast circled in red. Here is our epithelium along
the top & so above this epithelium could be the lumen of an organ, the
lumen of the stomach or it could be the outside of the body & then when
you go in from that epithelium, then you enter this region of connective
tissue here. So this contains the cells that make that connective tissue, the
fibroblasts, but this is also where you’d also find your muscle cells, the
neurons, the immune cells, for example here is a macrophage, a white
blood cell, that may have left the bloodstream, here is a capillary running
through this extracellular matrix that may have left this to go & fight an
infection like we learned about last day.
- So we’ve learned about epithelia, neurons, muscle cells, immune cells.
Here we’re talking about the extracellular material that all these cells are
- So these extracellular networks, they include these 2 types right here as
listed in the slide.
- Diagram: The basal lamina is shown in yellow. This is a muscle cell, a
multinucleated cell, so here are the brown nuclei in this single cell & it’s
surrounded in direct contact with the cells is this basal lamina. Here’s an
epithelium, so in direct contact with the base of these cells is the basal
lamina below. Here are specialized cell types in the kidney – here we
have these 2 cell types, one lining the blood & the other one lining the
urine – they are separated by this basal lamina so their basal side is in
contact with this very tightly woven sheet. Just outside this very tightly
woven sheet is a looser meshwork & this is what you call connective
tissue represented by the green dashes in the diagram.
- In addition to these 2 types, connective tissue also forms larger, more
specialized structures so tendons, bones, & cartilages as well. These will
surround all of cells, these 2 types, the basal lamina & the connective
tissue, but then also within that space b/w tissue we’ve got bones in there,
we have tendons connecting the bones to muscle so we can move our
- So the ECM does a couple of things, as listed in the slide.
- All the cells & tissues that are engaging with this ECM, it provides a
- In terms of the effects on tissue structure, this is basically the physical
aspects of the extracellular matrix. To impact a cell, you really need to
signal into a cell so how does the ECM send signals inside the cell to
change these properties here (listed in the cell) – we’ll talk about that in
the next lecture.
- Reinforced concrete has some similarities to the ECM – they both
provide tensile strength & resistance to compression. So by tensile
strength, we mean the resistance to sheer forces, an impact that would try
to bend that tissue whereas the compression is just compressing it from
the outside & withstanding that pressure from both sides.
- Reinforced concrete is made up of 2 parts: we’ve got the concrete part
which is basically like rock & then on the inside we have metal cables
running through that reinforced concrete. With the 2 elements here of the
rock & these cables, this provides tensile strength & resistance to
- So if we broke this reinforced concrete, look at its 2 parts separately. If
we only had the rock itself, we’ve all seen sculptures from ancient Greece
& Rome & those are made out of rock so you’re not going to be able to
compress those sculptures – you can press on it all you want but you’re
not going to be able to compress them. But those sculptures are not really
good at resisting sheer force – we’ve all seen sculptures that are missing
their heads, arms, & so on, b/c something has been knocked over, they’ve
hit something & that’s knocked off the head. So rock is very good at
resisting compression but not as good as resisting sheer forces, pulling
forces, or knocking forces. Now if we looked at just the wire alone,
compare that to a chain linked fence – that is very resistant to pulling
forces, so you can pull on a chain linked fence but you’re not going to be
able to break it very easily but we have all seen chain linked fences that
are completely compressed – people have stepped on the chain linked
fence to make a pathway through & that fence could be completely
- So each of them give these separate properties – when you put these 2
together, you have resistance to tensile strength from these cables &
resistance to compression from the rock & we’ll see the same elements
adhere in the ECM that gives this sort of structural support to our bodies.
- So you can see that the ECM plays a key role in giving tissues structure
b/c of some diseases associated with extracellular matrix molecules. So
here he’s just listed a few.
- These are defects in collagen – so this is a fibrous protein that would be
analogous to the cables in that reinforced concrete.
- Scurvy: If you aren’t eating enough Vitamin C, this collagen will be
weakened & there is a weakening of the tissues. The first time people saw
that this was a defect was when Europeans started traveling across oceans
to travel to North Americas – they would spend so much time out at sea
that their diets were just horrible & they would come down with this
disease called scurvy, then they would start to take cartons of limes along
with them & eat them & they realized that they were no longer getting
scurvy – the vitamin C in the lime was curing that scurvy.
- Gene mutations can also lead to defects in collagen, so these will lead to
weakening of bones, fragile skin & blood vessels, defects in the joints &
also defects in the kidney as well. So we’re losing structural support from
all these important parts of the body with these diseases.
- GAGs are acting like the filler in the ECM – they are like the stone.
- What are the structures of these molecules & how are they generated by
- We’ve learned a lot about proteins, another major component of cells
are lipids, these are sugars, they’re disaccharides.
- The disaccharide subunit involves an amino sugar combined with uronic
acid. N-acetyglucosamine combined with glucuronic acid is one example.
So there is a variety of different types of amino sugars and uronic acids
that can be paired up to make this disaccharide subunit of GAGs.
- Diagram: Here is the repeating disaccharide right here. You can see that
both of these structures look like sugars, they look similar to glucose.
You can identify the amino group so that is the amino sugar & these are
connected by their OH groups. So here they’ve got a covalent bond made
b/w these 2 & then there’s a covalent bond made to the next one
downstream so these then create sugars that can be up to 25,000 sugars
long & they’re all connected by covalent bonds going along their full
length. From this length you can sort of see how this molecule can start to
act like a filler – it’s a really long molecule so that’s one thing that gives
it its property of acting like a filler.
- Another thing is notice all these negative charges on the acid groups so
this is glucoronic acid so here is the acid group, so it’s negatively charged
– notice that these polysaccharide are also sulfated, so here’s a sulfate