Lecture 3 - Prof. Harris
October 29, 2015:48 AM
We are talking about how individual cells can be assembled into alrger
tissues or whole animals.
Look at the single cell:
This is really small. Fragile. Has a lipid bilayer. PM surrounding it.
Cytoskelton within i.
How does this cell form that mouse? And give the physical integrity it
One answer to the Q is that cells are orgnized into different cell
These cells are connected to on another: forms a layers of cells: and
behoind these they have cytoskelton netwroks we talked: these
cytoskeltons are conencted to cell adhesion complexes which
connects to its neighbor which also has another adhesion complex
If you look at this cellthere is a hige protein imteraction complex: bl
filament to adhesion complex --> blue filament to black adhesion
complex --> etc
This is spanning the nentire tissue and it can support the whole
This is beneath the eoithelial tissue is the conective tissue. This is
where the immune cells crawl through to helo protece the cell from
Physical structure of the connective tissueis made form ECM. These
are polymers of sugar found outside the cell. In a similar way creates
There is a huge structure of cells which resists complressoion and
pulling foces. By having protein interac ton through this Epi. Cells it
gives a larger physical siupport to tissues that make up the body
These epithelial tissues within them the cells are directly cononected
and they have the minimum ECM beneath them. A strip of yellow
Connected tissues we have individual cells and they are disperesed
within the ECM.
BIO230 Page 1 We focus on epithelial structure and why its important.
Epithelia forms barriers which is critical for our organ structure and
For the skin speration is between the external and internal
Organs: the lumen and cell
You can imagine your own body startig from one point and to antoher
point and ask what tisse structures do you pass. You pass skin -->
epithelial clls --> conective tissu (bones, tissue, ECM, tendons) -->
epithelium (forms our gut ) --> lumen of our gut.
You can see this in the human abdomen. Epithelium is forming the
organ and skin, and between the epithelium its the ECM
BIO230 Page 2 There are multiple junctions in epithelia which gives them structural
and functional properties
1. Anchoring jnctions: can connect the ECM and the cytoskeleton and
actin networks inside the cell. These junctions are formed from,
integrins. Gives a tight connection to the ECM.
a. Cell cell anchoring jucntions: receptors passing between,
interactin gwith the cell on the other side. Inside you have
connections to the cytoskelton/actin netwroks.
b. Adherenc: desmosomes. Both of these are based on adherence
These connect the epithelium cells together. There are occluding
juntions : seals the spaces between te epithelium cells. Forms a strong
barrier form one side if the epithelium sheet to the other.
Forms channels between the cells. Allows the cell to communicate
between one another and share resources. Small molecules can
pass through these to communicare or share resources.
Anchoring junctions between epithelium cells.
Imagine you are standing inside the single epithelium cell and you
can see a band of actin on the cytoplasmic face of the PM. The red
filamnets are actin filaments which are connected to the adhesion
receptors which reach out and interacts with the adhesion recptors
oon the oppostie side.
Analogy: brick. Cytoskelton gives the brick a strucyture. The adhesion
cmolex between the bricks can act like mortor to start creating the
bur=icks togethr to form the 2D…?
EM of the epithelium: yellow highlighted parts: plasma mebrane
from one cell and the PM from the othere there are space and very
specific distance between them.that is because there are specific
receptors interacting with them. Inside you can see the cytoskelton
which supports the junction
Single epithelium cell.
BIO230 Page 3 The way that caherens do the functio is by forming clusters. There is
one single cadherin protein which reach out ad interacts with
cadherin moelcules in the other cell in clusters.
There are individual molecules adding up to a large force. The
cadherin molecules reach out and interact with each other in 2 main
ways. One is that they reach out through the extra celular space and
binds homophillically. --> like with like.
If it was E cadherin it binds to E cadherin on the other sie
Reaches out and
interacts with the
There are two main ways
1 they reach out and interact with each other homophilically: like
with like. E cadherin binds to e cadherin on the other side.
Homophillic interactions Imagine the region from crystal structure there There is a specific
Amino acid sequence which loops and pokes into the hole on the
Extracellular oppostie sice and reaches out and mediates the molecule mechains,
The cytoplasmic side there are adapter proteins which links the
receptors to the actin cytoskeleton.
Overall startegy for the anchring junction is similar for the
organizstion seen in integrins: we have an extracellular receptor
which binds to something on the outside and adpators which links it
to the cytoskelton within
BIO230 Page 4 Why are adherence juncitons importatn?
Adherence junctions can be regulated very specifically.
The brick and mortar analogy falls apart. We can see how this sheet of
cells can move dynamically in the early dvelopment of an embryo. Look
how it still remains connected with one another and the sheet remains
That’s when the brick wall falls apart because the bricks will fall apart.
These tissues can be sculpted during development.
In the next embryuo there is a mutation in one of the key adherence
The movement is attempted, suddenly lose contact with one another
and looses its intergrity and idsintergrates (next slide)
BIO230 Page 5 This same role can be seen in adult tissesu and cancer tisseus.
The epithelial of normal cell is well organized.
In caner tissued there is an disorganziation like what we saw in the
Loss is epithelium is a hallmark of cancer.
Cadherins are important for holding the structure together and
suppressing the progression of cancer.
Those are number of ways why epithelial structure is important.
The polarity of ept. Cells
It means that one side of the cell is different from the other side.
The organ lumen or the animal surface
When I use polarity it means differences between one side of the
strucure is different from the other. There are two main parts of the
PM of the cell which is differnet.
We have an apical surface, and this will either face the lumen of the
organ or the outside of the body.
The basl surface faces the underlying tissue which is the connective
tissue we were talking about. Connective tissue is always connected to
the basla surface and the other side faces the lumen of an organ or the
outside of the body
BIO230 Page 6 Epithelial barriers are not absolute, but they can be regulated., the cell
controls them because of its polarity.
Epithelial polarity is used to gather sugar from the gut in this:
Gathering sugar from the gut. Apical surface faces the lumen where it
has glucose from digested food. You have digestive environement adna
The body wants to gather the glucose but not the other parts.
So one critical component is the tight junctions formed between the
apical embrane and the basolateral meembrane. They seal from any
material from passing in between the cells. So that forces transport to
go THROUGH THE CELL. So there are plasmam mebrane channel which
will only accept glucose and reject other stuff from the gut. So there is a