Download Collagen and Collagenous Tissues Collagen

Topic 6:
Collagen and Collagenous Tissues
Collagen: Overview
• Structure of collagen fibrils
– Biochemistry
– Molecular Biology
– Morphology
• Biomechanics of collagenous tissues
– 1D
Ligament/Tendon
– 2D
Intestine/Blood Vessels/Pericardium
– 3D
Skin/Heart
Molecular Structure
• Triple Helix (Gly-X-Y)N
– X=proline
– Y=hydroxyproline
• Triple helix +
crosslinks:
Structure gives rise to
a material that is very
stiff and stable
• Crosslinks (covalent
bonds) occur
between the ends of
molecules
• Collagen is the primary structural protein
in the body
• Collagen is the most prevalent protein
comprising ~30% of ALL proteins
• Collagen is highly conserved between
species (i.e. has not undergone many
evolutionary changes)
Band Spacing
D=670 Å
FIBRIL
Hole Zone (0.6D)
Overlap Zone (0.4D)
MICROFIBRIL
3000Å (4.4D)
COLLAGEN
MOLECULE
15Å Dia
104Å
TRIPLE
HELIX
PRIMARY
STRUCTURE
IN α-CHAIN
8.7Å
Glycine
Y
X
Glycine
Y
Collagen: Molecular Biology
•
•
•
•
>20 different types have been identified
characterized by different α
- chains
each α
- chain is coded by a different gene
exons are often 54 bp long
– 3 bp in a codon
– 18 amino acids
– 6 sets of Gly
- X
- Y
Homotrimer
Type III=(α1(III))3
Collagen Molecular Structure
Heterotrimer
Type I=(α1(I))2α2(I)
Type XI=α1(XI)α2(XI)α3(XI)
• Molecules arranged in
staggered pattern
• X
- ray diffraction or
electron microscopy
give rise to a
banded pattern
• Also relatively resistant
to enzymatic
breakdown
X
Collagen Types
Classifications
Fibrillar
I
II
III
V
VI
Fibril Associated IX
XII
XIV
Network Forming IV
X
VIII
Filamentous
VI
Anchoring
VII
Examples
Tendon, Skin, Ligament, Heart
Cartilage
Skin Vessels, Tendon, Heart
Fetal Membranes - Assoc w/ Type I
Cartilage - Assoc w/ Type II
Cartilage, Cornea
Embryonic Tendon
Fetal Skin & Tendon
Basement Membrane
Hypertrophic Cartilage
Descemet’s Membrane
Vessels, Skin
Anchoring Filaments
Fibrillar Collagen (I (mostly), III) has greatest stiffness
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Material Properties
Material
Collagen
Steel
Wood
Rubber
Bone
Elastin
Silk
Stiffness
1 GPa
200 GPa
10 GPa
1000-1400 kPa
18 GPa
500-600 kPa
10 GPa
UTS
100 MPa
1000 MPa
100MPa
125 MPa
100-500 MPa
But that's not enough information to predict
behavior in tissues...
Tissues are composites
Complex organization
Complex boundary conditions
Ligament/Tendon - 1D:
Physiological Functions
• connect bones together (Ligament)
• connect bones to muscle (Tendon)
• Transmit forces
• Aid in smooth joint motion
• Absorb impacts/stresses
• Prevent large displacements such as
dislocations
• Basically uniaxial loading elements
Tendon Hierarchy
Tissue Structure-Function
Structure
Architecture
Anatomy
Function
Constitutive
Law
Τ=f(Ε)
Tissue
Stress-Strain
Force-Elongation
Model
Material Properties
Boundary Value Problems
Conservation Laws
Ligament/Tendon:
Structure/Biochemistry
• Loading
– Fibers are parallel to load axis
• Organization
– some fascicular organization
– Unloaded = crimped
– loaded = straight
• Composition
– Collagen 75-80%
– Elastin ‹5 %
– PG 1-2%
Knee Ligaments:
Anatomy
Lateral
Femur
Medial
Quadriceps
Tendon
Patella
Lateral
Collateral
Ligament Menisci
(LCL)
Medial
Collateral
Ligament
(MCL)
Posterior
Cruciate
Ligament
(PCL)
Fibula
Anterior
Cruciate
Ligament
(ACL)
Tibia
Patellar
Tendon
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Ligament/Tendon
Histology
Ligament/Tendon:
Mechanical Properties
100
Tensile Strain
Tensile Stress
Stress (MPa)
75
50
n
Ta
25
0
0
2
n
ge
tM
ul
od
4
6
Toe Region Linear Region
Rabbit MCL
us
8
Yielding and
Microfailures
Strain (%)
10
Catastrophic
Failure
Rabbit ACL
Ligament/Tendon:
Structure/Histology
Intestine - 2D:
Physiological (mechanical) Functions
• Allow distension when digesting food
• Prevent over- stretching and consequent
damage to other internal organs
• FINITE DEFORMATIONS
Loaded
Unloaded
Intestine: Structure
• Crimped
• 2 primary planes
• doesn’t need to be as complex as skin because
deformations are predictable
Blood Vessels - 2D
Physiological Function
Allow distension with increasing blood pressure
Blood Flow
Hydrostatic Pressure
Prevent damage to endothelial cells and smooth muscle cells
Circumferential axis of intestine
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Blood Vessels: Structure
• Typically Blood vessels have more type III collagen
(which is more compliant)
• Also have a lot of elastin
• collagen fiber diameter ~50nm
1D and 2D Collagenous Tissues
• Collagen is organized in tissue in such a way
that it allows increased deformations in the
tissue without actual stretching/straining
collagen very much
• The organization is usually such that the axes
of the fibers are oriented with the axis of
maximal forces
Skin:
Structure
• Collagen
65- 70 %
(more type III than ligament)
• Elastin
5- 10 %
• Proteoglycans
1.5- 2 %
Blood Vessels:
Collagen straightens with distension
Measure Extinction Angle with
Polarized Light Microscopy
Theoretical Predictions with
Analysis of Sine wave
Skin – 3D:
Physiological Functions
• Protect body from invasion
• Withstand repeated in
- plane stresses
(knee
- elbow)
• Transmit impacts into plane stresses
• Problem: not a well defined direction
• Solution: have collagen oriented in
random direction
Skin: Mechanical Properties
• More compliant than
ligament or tendon;
needs to be for its
functions.
• orientation of coiled
fibers change with
load
• collagen is stiffer than
elastin but has greater
hysteresis (absorbs
more energy)
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Skin: Collagen and Aging
Skin: Elastin and Aging
• collagen crimp decreases with age; stiffness increases
• elastin crimp increases with age; decreasing recoil
• Is this a mechanical explanation for wrinkles?
Young
Adult
Old
Heart - 3D collagen ECM:
Physiological Functions
• Pump Blood
• Allow myocytes to stretch, but prevent
overstretch
• More complicated because heart is pumping
• Keep blood vessels open
• Transmit contractile forces to chamber
• Elastic recoil
• Lateral slipping - shearing deformation
Heart: Endomysial Collagen
Link adjacent myocytes at
Z-line of sarcomere
Maintain patency of
capillaries
Young
Adult
Old
Heart:
ECM Structure
• Extracellular Matrix
Perimysial
Weave Network
– only 5% of heart wt.
– ~95% collagen (I, III)
• Hierarchical
Z-line of Sarcomere
– Endomysial (between,
around cells)
Myocytes
– Perimysial (groups
Coiled
Perimysial
cells together)
Fiber
Endomysial Weave
– Epimysial (surrounds
Endomysial Struts
myocardium)
Heart: Perimysial Network
Organize myocardium into laminar sheet architecture
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Heart: Coiled Perimysial Fibers
Heart: Pathology
Infarction:
• Myocytes die
• Collagen increases
in density
• Coiled structure
looks more 2dimensional
Protect myocytes from overstretching
Major contributor to passive stiffness
Heart: Infarction
Mouse heart
with MI
Heart: In vivo Strain Analysis
Mouse heart sections
In vivo Strain on Infarct Surface
Area strain
1.15
Bgn+/0
Bgn-/0
Explanted human heart tissue from transplant recipient
Looks like a ligament
or tendon?
3 points on infarct surface tracked in video frames
Infarct Collagen Fibrils
During roughly one
heart beat
1.10
1.05
1.00
0.95
-0.02 0.00 0.02 0.04 0.06 0.08 0.10 0.12
Time (sec)
Infarcts of proteoglycan-knockout mice appear stiffer than infarcts of
normal mice
Cross section
Longitudinal, showing striped
pattern
Not as uniformly organized as in healthy tissue
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Sarcomere Length vs. Pressure
Cardiac Collagen:
Biomechanics
2.25
2.2
SL (µm )
2.15
2.1
2.05
2
Data from Grimm et al. 1980
1.95
0
25
50
75
100
Pressure (mmHg)
•
Conclusions
• Collagen is a key structural protein in the body
• By organizing this stiff material in different ways,
the body achieves may different functions
– 1D ligament; very stiff; less crimp
– 2D skin- versatile organization
intestine- less versatile
vessel- less versatile
– 3D heart- complex organization, large
deformations
Collagen fibers reach near maximal straightening
coincident with maximal sarcomere length
Collagenous Tissues: Summary of
Key Points
• Collagen is a ubiquitous structural protein with
many types all having a triple helix structure that is
cross- linked in a staggered array.
• Some of the most common collagen types are
fibrillar and the collagen can be organized in 1-D,
2-D or 3-D in different tissues to confer different
material properties.
• The 1-D hierarchical arrangement of stiff collagen
fibers in ligaments and tendons gives these
tissues very high tensile stiffness
• The 2-D arrangement of collagen fibers in tissues
such as blood vessels and intestine is often quite
wavy or disordered to permit higher strains
Collagenous Tissues: Key Points
(continued)
• Crimping, coiling and waviness of collagen matrix
gives the tissue nonlinear properties in tension.
• Collagen structure in tissues changes with
disease and ageing.
• The hierarchical cardiac collagen matrix
organizes cardiac muscle fibers in three
dimensions. Interstitial fibrillar collagen in the
heart wall contributes to tissue stiffness during
filling.
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