The Extracellular Matrices
Part II.
2. Elastin fibers.
3. Proteoglycans (PG) and glycosaminoglycans
(GAG).
4. Cell-adhesion molecules (CAM).
1
Elastin fibers
? A network of randomly coiled macromolecules.
No periodicity. Highly extensible chains.
? Rubber-like elasticity is complicated by
hydrophobic bonding effects.
? Interaction of hydrophobic (nonpolar) AA with
water leads to hydrophobic bonding. Primarily
entropic, not energetic, bonding between
molecules. It forces nonpolar macromolecules,
such as elastin, to adopt a compact, rather then
extended, shape in hydrated tissue.
? Stretching of elastin fibers leads to large entropy
loss due to reduction in chain configurations and
increased “ordering” of water molecules against
nonpolar AA. Spontaneous retraction.
? Elastic ligament of neck. Blood vessel wall.
2
The Hydrophobic bond
3
?G = ?H ? T?S
Equilibrium when ?G = 0. G is Gibbs’ free energy, the
enthalpy is H = E + PV, T is absolute temperature and
S is the entropy. The process goes spontaneously
from left to right when ?G < 0. Find the position of
thermodynamic equilibrium for a well-known example
of insolubility:
CH
4
in benzene → CH
4
in H
2
O
The experimental data show (all units in calories per
mol): ?G = ? H ? T ? S
+2600 = ?2800 ? 298(?18)
+2600 = ?2800 + 5400
Conclusion: Insolubility of paraffin in water due to
entropy loss, not to enthalpy change! (Kauzmann)
Historical models of cell membrane structure
Image removed due to copyright considerations
Image removed due to copyright consi erations
4
Cell
membrane
showing
bilayer
structure
5
Elastin fibers in the relaxed aorta.
Elastin macromolecules are random coils
tied together to form a 3-dimensional
(insoluble) network.
Images removed due to copyright considerations
Images removed due to copyright consi erations
Macromolecules coil upon themselves due to
high content of nonpolar (hydrophobic) amino acids that mediate
withdrawal from polar medium (aqueous buffer) and promote
bonding within chains. These networks stretch extensively like all
rubbers.
6
Proteoglycans (PGs) and
glycosaminoglycans (GAGs)
? A proteoglycan is a polypeptide chain (proteo) with
polysaccharide (glycan or GAG) side chains.
? Primary structure modeled as an alternating
copolymer of two different glucose-like units, one of
them an acidic sugar-like molecule, the other an
amino sugar with a negatively charged sulfate group
(except hyaluronic acid that is not sulfated).
? Electrostatic interactions between charged groups in
GAG side chains of PG responsible for about 50% of
stiffness of articular cartilage (Grodzinsky et al.).
7
Proteoglycans (PGs) and
glycosaminoglycans (GAGs)
Images removed due to copyright considerations
Images removed due to copyright consi erations
8
9
Γλυκοσαμινογλυκανε?
Glycosamino-
glycans
disaccharide repeat unit
Image removed due to copyright considerations.
Diagram of Chondroitin 4-Sulfate
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Diagram of Dermatan Sulfate.
Image removed due to copyright considerations.
Diagram of Heparan Sulfate.
10
Γλυκοσαμινογλυκανε?Proteoglycans and glycosaminoglycans
repeat unit of chondroitin 6-sulfate
a proteoglycan
Image removed due to copyright considerations.
Cell-adhesion molecules
? Cell-matrix interactions involve binding of
transmembrane proteins (integrins) on
specific sites (ligands) in ECM molecules
such as fibronectin, laminin and collagen.
Example: integrins of contractile fibroblasts
bind to fibronectin molecules that are
attached to collagen fibers (fibronexus).
? Integrins connect with proteins in the cell
cytoplasm and a signal is transmitted to or
from the nucleus.
11
12
Μια ιντεγκρινη συνδεει το εσωτερικο
του κυτταρου(κατω) με ΕΚΜ (πανω)
An integrin “connects” the interior of the
cell (cytoplasm) with the ECM outside it
After Hynes, 1990.
Cell Membrane
Phospholipid
molecule
Bilayer structure
of cell membrane
viewed by
electron
microscopy
duplicate of Intro s.14 – 2 redraws, 1 delete
Cell
membrane
showing cell
surface
receptors
(integrins)
13
Image removed due to
copyright considerations.
Cells pull matrix (thin silicone film),
causing buckling (Harris et al.)
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Image removed due to copyright consi erations
14
Location of fibronectin binding sites (Hynes, 1990)
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Image removed due to copyright consi erations
15