Molecular, Cellular & Tissue Biomechanics

Goal: Develop a fundamental understanding of

biomechanics over a wide range of length scales.
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Biomolecules and intermolecular forces
Single molecule biopolymer mechanics
Formation and dissolution of bonds
Motion at the molecular/macromolecular
level
MOLECULAR MECHANICS
Structure/function/properties of the cell
Biomembranes
The cytoskeleton
Cell adhesion and aggregation
Cell migration
Mechanotransduction
CELLULAR MECHANICS
TISSUE MECHANICS
Molecular structure -->physical properties
Continuum, elastic models (stress, strain,
constitutive laws)
Viscoelasticity
Poroelasticity
Electrochemical effects on tissue properties
Fall, 2006
1
Some Learning Objectives
1. To understand the fundamental concepts of mechanics
and be able to apply them to simple problems in the
deformation of continuous media
2. To understand the underlying basis for the mechanical
properties of molecules, cells and tissues
3. To be able to model biological materials using methods
appropriate over diverse length scales
4. To be familiar with the wide spectrum of measurement
techniques that are currently used to determine
mechanical properties
5. To appreciate the close interconnections between
mechanics and biology/chemistry of living systems
20.310, 2.793, 6.024
Fall, 2006
Biomechanics of tissues
Mechanics Biology
I. Linear elastic behavior I. Biochemical and
molecular biology of
II. Viscoelasticity
ECM molecules
III. Poroelasticity
A. Collagen
IV. Electrochemical and superfamily
physicochemical properties
B. Proteoglycan
superfamily
C. Other glycoproteins
II. Nanomolecular
structures <-->tissue
III. Mechanobiology
20.310, 2.793, 6.024
Fall, 2006
2
Some preliminaries
Equilibrium -- balance of forces
concept of a stress tensor
Compatibility -- relations between displacements and
strains or deformation
normal strains; shear strains; strain tensor
Constitutive laws
stress -- strain
Youngs modulus; Poissons ratio, shear modulus
linear, isotropic, elastic materials
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
Force balance in a single cell
Desprat et al.,
Biophys J ., 2005.
Figure by MIT OCW.
3
Stress distributions along the basal surface
of a resting cell
20.310, 2.793, 6.024
Fall, 2006
Several material testing methods
Linear extension Linear shear
Biaxial tension
Cone-and-plate rheometer Confined compression
20.310, 2.793, 6.024
Fall, 2006
4
Graphical image of stress distributions on a cell surface removed
due to copyright restrictions.
Hu, et al., AJP Cell, 2003
Tissue properties: common simplifying
assumptions
Linear -- the elastic modulus is constant,
indpendent of strain amplitude
Homogeneous -- the material is spatially
uniform
Isotropic -- the material exhibits the same elastic
properties in all directions
Time-independent -- stresses and strains are
uniquely related, independent of rate of strain
20.310, 2.793, 6.024
Fall, 2006
Constitutive laws for a linear elastic,
isotropic material
= ) + 2G
1

11
(
11
+
22
+
33 11
(
11
=

11

22
+
33
)

22
=
11
+
22
+
33
) + 2G
22
(
1
( ) = ) + 2G
22
=
E

22

11
+
33

33
(
11
+
22
+
33 33
1

12
= 2G
12

33
=
E

33

11
+
22
)

13
= 2G
13
(

12
(1 + )
12

23
= 2G
23

12
= =
2G E

13
(1 + )
13
2G E
= = = =
13
2G E
1 2

(1 + )(1 2 )

23
(1 + )
23

23
= =
2G E E = Youngs modulus = Lame constant
= Poissons ratio G = shear modulus
20.310, 2.793, 6.024
Fall, 2006
5





20.310, 2.793, 6.024
Fall, 2006
1.E+00
1.E+02
1.E+04
1.E+06
1.E+08
1.E+10
1.E+12 DIAMOND
STEEL
BONE CONCRETE
SILK F-ACTIN
TENDON WOOD
TUBULIN
CONTRACTED SKELETAL MUSCLE
ELASTIN
RELAXED SKELETAL MUSCLE
COLLAGEN GELS
LUNG PARENCHYMA FIBROBLAST CELLS
ENDOTHELIAL CELLS NEUTROPHILS LYMPHOCYTES
Values of the elastic or Youngs modulus (E) for
various materials
20.310, 2.793, 6.024
Fall, 2006
Linear? Unidirectional tensile tests
Stress-strain behavior of a peptide hydrogel
Linear behavior up to
fracture
Relatively low
toughness due to small
fracture strain
a b needle needle
peptide
matrix
peptide
matrix
plastic
mesh
6
Figure by MIT OCW. Adapted from Leon, et. al., 1998
Constant E
s
11
e
11
0
0.005 0.01 0.015 0.02 0.025 0.03 0.035 0.04
10
20
30
50
60
40
Stress
(N/m 2)
>
Strain
7
Linear? Elastin is one of
main structural
components of tissue
Linear; little hysteresis.
Provides the
stretchiness of tissues.
Combination of single-
molecule characteristics
and microscale structure.
20.310, 2.793, 6.024
Fall, 2006
Linear? ACL -- different strain rates
20.310, 2.793, 6.024
Fall, 2006
Figure by MIT OCW.
Figure by MIT OCW.
Slow Medium Fast
Range of linearity
E = ds/de = 10
9
Pa
2 4 6 8 10 12 0
80
60
40
20
Strain(%)
S
t
r
a
s
s

(
M
P
a
)
Control
100
80
60
40
20
0
5 10 15 20
Specimen
fixed at zero
stretch in 10% formalin
ELASTIN
Lig. Nuchae denatured
% Strain = (L/L
0
)*100
S
t
r
e
s
s

(
k
P
a
)
The stress-strain curve of elastin. Data from Fung and Sobin (1981).
Linear and Isotropic? Right tibia
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
Canine aorta showing elastic fiber content
8
Figure by MIT OCW.
Scanning electron micrographs showing a low-power view of dog's
aorta and a high-power view of the dense network of longitudinally
oriented elastic fibers in the outer layer of the same blood vessel.
Images removed due to copyright restrictions. See Haas, K. S.,
S. J. Phillips, A. J. Comerota, and J. W. White. Anat. Rec.
230 (1991): 86-96.
250
200
150
100
50
0
0
1 2 3
4
S
t
r
e
s
s

(
M
P
a
)
Strain (%)
RA-direction
Sample no.
Sample no.
BA-direction
6
6
1
1
3
2
2
4
4
5
5
Longitudinal
direction
Radial direction
20.310, 2.793, 6.024
Fall, 2006
Collagen fiber arrangement in skin and cornea with
alternating directions
20.310, 2.793, 6.024
Fall, 2006
Homogeneous? Only rarely
9
Electron micrograph of a
cross-section of tadpole skin. The
arrangement of collagen fibrils is
plywoodlike, with successive layers
of fibrils laid down nearly at right
angles to each other. Image
removed due to copyright
restrictions.
Electron micrographs of parallel
collagen fibrils in a tendon and the
mesh work of fibrils in skin removed
due to copyright restrictions.
Figure by MIT OCW.
Tendon
Fascicle
Tendon Hierarchy
X ray EM X ray EM X ray EM
SEM
EM SEM
OM
SEM
OM
Evidence:
X- ray
Reticular
membrane
Fascicular
membrane
Waveform or
crimp structure
Fibroblasts
Tropocollagen
35 staining
sites
640
periodicity
15 35
o
A
o
A
o
A
o
A
o
A
o
A
100-200 500-5000 50-300 100-500
Size Scale
Subfibril Microfibril
Fibril
20.310, 2.793, 6.024
Fall, 2006
Histological cross-section
of a diseased carotid artery
stained for smooth muscle
cells.
Elastic response
initially, then stiff,
collagen response at
high degrees of
extension.
H =hypertensive
High wall stress
leads to functional
remodeling.
Time-dependent? Peptide gels Pre- and Post-
100 M KCl
1000 M KCl
Storage Modulus (G)
Loss Modulus (G)
Gelation. Properties can change with time.
1%wt KFE12
20.310, 2.793, 6.024
Fall, 2006
10
Figure by MIT OCW.
Figure by MIT OCW.
1000
100
10
1
1
0.1
0.01
Oscillatory Frequency (rad/sec)
5 10
M
o
d
u
li (P
a
)
1000
100
10
1
1
0.1
0.01
Oscillatory Frequency (rad/sec)
5 10
M
o
d
u
li (P
a
)
100 M
1000
Cl
Cl
Storage Modulus (G')
Loss Modulus (G")
Primary data for gel formation of 1wt % KFE12 equilibrated with
(a) 0.1mM NaCl and (b) 1.0 mM NaCl. The storage modulus (squares),
G', and loss modulus (circles), G", are plotted against oscillatory frequency
on log-log scales.
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0 100 200 300 400
Group N
Group H
Pressure (mm Hg) Pressure (mm Hg)
R
e
l
a
t
i
v
e
r
a
d
i
u
s
10 90 170 250 330
0.1
1
10
Incremental modulus:
E = d/d
I
n
c
r
e
m
e
n
t
a
l
e
l
a
s
t
i
c
m
o
d
u
l
u
s
(
M
P
a
)
Stiffening
Shear Modulus of cartilage. Modulus can be
frequency-dependent (Dynamic @ 0.5Hz, 0.8% strain)
20.310, 2.793, 6.024
Fall, 2006
Other complications:
Surface tension in
lung parenchyma
Surface tension effects
20.310, 2.793, 6.024
Fall, 2006
11
Images removed due to
copyright restrictions.
Figure by MIT OCW.
Figure by MIT OCW.
1
0.75
0.5
0.25
0
0.01 0.1 1
10
12.5
15
17.5
20
2.5
2
1.5
1
0.5
0
Dynamic G
Equilibrium: G
Ionic Concentration, M
Dynamic Phase
Dynamic G
Dynamic G
Magnitude, MPa
Phase Angle (degree)
(Mean
(Mean
+
-
+
-
S.D, n= 4,
S.D, n= 3.6)
f =0.5Hz, g = 0.8% )
Equilibrium G, MPa
q.G
200
150
100
50
5 10 15 20
Liquid Inflation
L
i
q
u
i
d
A
i
r
Effect of
surface
tension of
gas-liquid
interface
Effect of
collagen at
high degrees
of extension
Nearly linear response
at small extensions
Air Inflation
Relaxation Pressure
L
u
n
g

V
o
l
u
m
e

(
m
l
)
Von Neergaard Experiments
20.310, 2.793, 6.024
Fall, 2006
Striated
Other
complications:
Active
contraction
Underlying basis for mechanical properties
Extracellular matrix, cartilage, and tendon are largely
comprised of:
collagen
elastin
proteoglycan
(role of constituent cells??)
20.310, 2.793, 6.024
Fall, 2006
12
Figure by MIT OCW.
Figure by MIT OCW.
Figure by MIT OCW.
A
B
C
D
A- resting
B- max contraction
C- active component
0
0
0
5 10 15 20
20
25
25
30 35
50 75 100
100
125 150 175
40
60
80
(mm)
(%)
Muscle length
T
e
n
s
io
n
(m
N
)
Caption:
A, resting tension; B, maximum tension produced by optimum stimulus; C, active tension (= B - A);
D, potentialed tension produced by successive stimuli.
The slightest resting tension was produced at 75% of the in situ length (20 mm). *
*
*
*
*
The optimum length, at which the active tension become maximum, is between 100% and 125% of the
in situ length.
The active tension declines almost symmetrically on either side of the optimal length.
The maximumn tension potentialed by the successive stimuti was attained at 75% of the in situ length.
Macroscopic view
120
100
T
e
n
s
i
o
n

(
%

o
f

m
a
x
i
m
u
m
)
80
60
40
20
0
1.0 2.0 3.0 4.0
Striation spacing (mm)
Many features of the length-tension relation are simply explained by the
sliding-filament theory.
The peak of the curve consists of a plateau between sarcomere lengths
of 2.05 and 2.2 mm.
Microscop
sarcomere
ic -
level
Typical elastic behavior for tissues containing
collagen and elastin
20.310, 2.793, 6.024
Fall, 2006
13
20.310, 2.793, 6.024
Fall, 2006
Collagen fibril formation
Figure by MIT OCW.
Figure by MIT OCW.
STRAIN, (L/L
0
)
T
E
N
S
I
L
E

S
T
R
E
S
S
,

(
F
/
A
)
Young's Modulus = /

Elastin
dominated
Failure
Linear Region
Toe Region
Collagen dominated
Synthesis of pro- chain
Self-assembly Of
Three pro- chain
2
1
4
5
3
6
7 8
9
Hydroxylation Of
Selected Prolines
And Lysines
Glycosylation Of
Selected Hydroxylysines
Propeptide
3 pro- chain
Procollagen Triple-helix
Formation
H
2
N
H
2
N
OH OH
OH
OH
OH
OH
OH
OH
OHOH
OH
OH
OH
OH
OH
Secretory vesicle
ER/Golgi compartment
Collagen molecule
Self-Assembly
Into Fibril
Aggregation Of
Collagen Fibrils To
Form A Collagen Fiber
Collagen fiber
Collagen fibril
0.5-3m
1
0
-
3
0
0
n
m
Procollagen molecule
Secretion Plasma membrane
OHOH
OH
OH
OH
OHOHOH
OH
OH
OH
OH OH OH Cleavage of
propeptides
The Intracellular and Extracellular Events Involved in the Formation of a Collagen Fibril
Collagen -- single molecule

characteristics
20.310, 2.793, 6.024

Fall, 2006

20.310, 2.793, 6.024

Fall, 2006
As of 2003, there
were 28 (!)
different types of
collagen
identified.
14
Figure by MIT OCW.
Figure by MIT OCW.
Major Collagen Molecules
Type Molecule composition Structural features
Representative
tissues
Fibrillar collagens
[ 1(I)]
2
[ 2(I)]
[ 1(IV)]
2
[ 2(IV)]
[ 1(VI)][ 2(VI)]
[ 1(IX)][ 2(IX)][ 3(IX)]
[ 1(II)]
3
[ 1(III)]
3
[ 1(V)]
3
Fibril-associated collagens
300-nm-long fibrils
300-nm-long fibrils
300-nm-long fibrils;
often with type I
390-nm-long fibrils
with globular N-terminal
domain; often with type I
Lateral association with type
I; periodic globular domains
Lateral association with
type II; N-terminal globular
domain; bound glycosami-
noglycan
Two-dimensional network
Skin, tendon, bone,
ligaments, dentin,
interstitial tissues
Skin, muscle, blood
vessels
Similar to type I; also
cell cultures, fetal
tissues
Most interstitial
tissues
Cartilage, vitreous
humor;
All basal laminaes
I
II
III
V
VI
IX
IV
Sheet-forming collagens
Cartilage, vitreous
humor
Figure by MIT OCW.
14
12
10
8
6
4
2
0
0
-0
50 100 150 200 250 300 350
The force-extension curve of a single
collagen II.
Cover glass
XY Stage
Trap Center
Laser light
Procollagen
Stretching a procollagen II molecule with optical tweezers.
Figure by MIT OCW.
20.310, 2.793, 6.024
Fall, 2006
Type IX collagen decorated with type II collagen
20.310, 2.793, 6.024
Fall, 2006
15
Figure by MIT OCW.
Figure by MIT OCW.
Type IX collagen
molecule
Fibril of type II
collagen
Stretch
Relax
Elastic Fiber
Single elastin
molecule
Cross-link
Short section
of a collagen
fibril
collagen molecule
300 X 1.5 nm
50 nm
1.5 nm
Collagen triple
helix
Contrast between elastin and collagen
20.310, 2.793, 6.024
Fall, 2006
Entropic elasticity
Proteoglycans (PGs) and
glycosaminoglycans (GAGs)
a) GLYCOSAMINOGLYCANS (GAGs) form gels
i) polysaccharide chains of disaccharide units
ii) too inflexible and highly charged to fold in a compact way
iii) strongly hydrophilic
iv) form extended conformations and gels
v) osmotic swelling (charge repulsion)
vi) usually make up less than 10% of ECM by weight
vii) fill most of the ECM space
viii) four main groups
a. hyaluronan
b. chondroitin sulfate and dermatin sulfate
c. heparin sulfate and heparin
d. keratin sulfate
20.310, 2.793, 6.024
Fall, 2006
16
Figure by MIT OCW.
Stretch
Relax
Elastic Fiber
Single elastin
molecule
Cross-link
b) Proteoglycans (PGs)
i) form large aggregates
ii) aggrecan is a large proteoglycan in cartilage
iii) decorin is secreted by fibroblasts
iv) PGs have varying amounts of GAGs.
v) PGs are very diverse in structure and content
vi) PGs and GAGs can also complex with collagen
vii) secreted proteoglycans have multiple functions
viii) PG/GAGs have important roles in cell-cell
signaling
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
17
Electron micrograph of proteoglycans in the extracellular matrix of rat
cartillage removed due to copyright restrictions.
See Hunziker, E. B., and R. K. Schenk. J Cell Biol 98 (1985): 277-282.
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
18
Figure by MIT OCW.
Figure by MIT OCW.
100 nm
GAG
Core Protein
Polypeptide chain
Short, branched
oligosaccharide
side chain
Decorin
(MW - 40,000)
Aggrecan
(MW - 3 x 10
6
)
Ribonuclease
(MW - 15,000)
Examples of a large (aggrecan) and a small (decorin) proteoglycan found in the extracellular matrix.
They are compared to a typical secreted glycoprotein molecule (pancreatic ribonuclease B). All are
drawn to scale. The core proteins of both aggrecan and decorin contain oligosaccharide chains as well
as the GAG chains, but these are not shown. Aggrecan typically consists of about 100 chondroitin sulfate
chains and about 30 keratan sulfate chains linked to a serine-rich core protein of almost 3000 amino
acids. Decorin "decorates" the surface of collagen fibrils, hence its name.
Aggrecan Aggregate
Core protein
Link proteins
Chondroitin sulfate
Hyaluronan
molecule
Keratin sulfate
1 mm
Schematic drawing of an aggrecan aggregate. It is composed of 100 aggrecan
monomers noncovalently bound to a single hyaluronan chain through two link
proteins that bind to both the core protein of the proteoglycan and to the
hyaluronan chain, thus stabilizing the aggregate.
20.310, 2.793, 6.024
Fall, 2006
Atomic Force Microscopy of Aggrecan
20.310, 2.793, 6.024
Fall, 2006
19
Figure by MIT OCW.
Electron micrograph of an aggrecan aggregate removed due to copyright
restrictions.
Images removed due to copyright restrictions.
Aggrecan Chondroitin sulfate GAG
Chains
(Fetal Bovine)
Ave. GAG length: ~36 nm
Inter-GAG spacing: 4-5 nm
(L. Ng, C. Ortiz, A. Grodzinsky)
Hyaluronan Molecule
Link Protein
N-terminal Hyaluronan-
binding domain
Keratan Sulfate
Chondroitin
Sulfate
Linking Sugars Aggrecan Core Protein
30
20
10
0
-10
0.5
1 1.5 2 2.5
Single Hyaluronan Molecule
F
o
r
c
e

(
p
N
)
Displacement (mm)
Atypical result of the force-displacement relationship from
the single hyaluronan molecule measurement.
Figure by MIT OCW.
Like charge repulsion accounts for a large fraction (~50%) of
the stiffness in tissues with high GAG content.
These effects can be eliminated either by shielding with
counter-ions or neutralization by changing pH.
+
+
+ +
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
Confined compression experiments
20
Figure by MIT OCW.
1.2
1
0.8
0.6
0.4
0.2
0.001 0.01 0.1 1
Electrostatic: GAG
other
E
q
u
i
l
i
b
r
i
u
m

M
o
d
u
l
u
s
,

M
P
a
Ionic Strength, M
Equilibrium Modulus of Adult Bovine Articular Cartilage
in Different Ionic Strengths
20.310, 2.793, 6.024
Fall, 2006
ADHESION PROTEINS
a) fibronectin
i) principal adhesion protein of connective tissues
ii) fibronectin is a dimeric glycoprotein
iii) fibronectin interacts with other molecules
b) laminin
i) found in basal laminae
ii) form mesh-like polymers
iii) has various binding sites
iv) assembles networks of crosslinked proteins
c) integrins
i) cell surface receptor, for attachment of cells to ECM
ii) family of transmembrane proteins
iii) two subunits, alpha and beta
iv) about 20 different integrins
v) binding sites for ECM components
vi) binding sites for the cytoskeleton and linkage to ECM
20.310, 2.793, 6.024
Fall, 2006
21
Figure by MIT OCW.
Some common proteoglycans
Proteoglycan
Approximate
molecular weight
of core protein
Type of GAG
chains
Number of
GAG chains
Location Functions
Aggrecan
Betaglycan
Decorin
Perlecan
Serglycin
Syndecan-1
210,000
36,000
40,000
600,000
20,000
32,000
Chondroitin
Chondroitin
Chondroitin
Chondroitin
Chondroitin
Sulfate +
Sulfate +
Sulfate/
Sulfate/
Sulfate/
Keratan
Sulfate
Dermatan
Dermatan
Dermatan
Sulfate
Sulfate
Sulfate
Sulfate
Heparan
Heparan
Sulfate
~130
1
1
2-15
10-15
1-3
Cartilage
Cell surface
and matrix
Widespread
in connective
tissue
Basal
laminae
Secretory vesicles
in white blood
cells
Fibroblast and
epithelial cell
surface
Mechanical support;
forms large aggregates
with hyaluronan
Binds to type 1
collagen fibrils
and binds TGF -
Structural and
filtering function
in basal lamina
Helps to package
and store secretory
molecules
Binds TGF -
Cell adhesion;
binds FGF
Fiall, 2006
20.310, 2.793, 6.024
Fall, 2006
The bundle thickness, mesh size, elastic modulus, and critical strain
as a function of R at cA = 11.9 M
22
Figure by MIT OCW.
Figure by MIT OCW. Adapted from Shin, J. H. et al. Proc Natl Acad Sci USA 101
(2004): 9636-9641.
R
0.2
R
0.3
R
2
I/R
0.6
10
0
10
0
10
0
10
-1
10
-1
10
-1
10
1
10
1
10
2
10
2
10
0
10
-2
10
-2
R

0
G
0
(Pa)

D (nm)
(m)
Bundle thickness
Mesh size
Shear modulus, G
Strain (
21
) at
which material
becomes nonlinear
Collagen binding
Cell binding
Heparin
C C
N
N
NH
2
Arg
Gly
Asp
HOOC
100 nm
The Structure of a Fibronectin Dimer
SS
SS
binding
20.310, 2.793, 6.024
Fall, 2006
Fall, 2006
The stress-strain relationships of F-actin networks formed with different FLN
mutants
We apply a prestress t o the network (Inset, single-headed filled arrow) and measure the deformation
(Inset, dashed arrow) in response to an additional oscillatory stress (Inset, double-headed filled arrow)
23
Figure by MIT OCW. Adapted from Gardel, M. L. et. al. Proc Natl Acad Sci USA 103
(2006): 1762-1767.
Figure by MIT OCW. Adapted from Gardel, M. L. et. al. Proc Natl Acad Sci USA 103
(2006): 1762-1767.
FLNa
FLNa
FLNa h(-)
FLNa h(-)
FLNb h(-)
FLNb h(-)
FLNb
FLNb
0.0 0.2 0.4 0.6 0.8 1.0 1.2
12
10
8
6
4
2
0
Strain
S
t
r
e
s
s

(
P
a
)
Strain,g
S
t
r
e
s
s
,

s
s
g
ds
dg
10
-2
10
-1
10
0
10
0
10
1
10
1
10
2
10
2
10
3
10
3
Prestress(Pa)
Differential
Stiffness (Pa)
20.310, 2.793, 6.024
Fall, 2006
20.310, 2.793, 6.024
Fall, 2006
Focal adhesion
complex
24
Figure by MIT OCW.
Figure by MIT OCW.
CYTOSOL
{
{
Lipid
bilayer
Cell coat
(glycocalyx)
Transmembrane
proteoglycan
Adsorbed
glycoprotein
Transmembrane
glycoprotein
Glycolipid
Simplified diagram of the cell coat (glycocalyx)
Sugar residue =
Fibronectin Extracellular
matrix
Cell membrane
Cytoplasm
Integrin
Focal adhesion
Actin
-
Actinin
Signals that control
cellular activities

Talin
Vinculin
Vinculin
Zyxin
Talin
Paxillin
Tensin
Ras
SOS
Grb2
FAK
Src
kinase
Paxillin p130
20.310, 2.793, 6.024
Fall, 2006
Viscoelastic models

k
F F

k
F F
1
k1
k2
F F
u
u
u2 u1
a)
b)
c)
Maxwell
Voigt
Standard linear
solid
Stress relaxation
Creep
Steady-state response to
oscillatory displacement
F(t ) = ku
0
exp(t / )
u(t ) =
F
k
1 exp t / ( )

= / k
E
*
( ) = E '+ iE"
Concept of a complex
elastic or shear modulus
Poroelastic materials
Governing equations:
1. Constitutive law

ij
tot
= 2G
ij
+
ij

ij
p
ij

11
x
1
u
1

U k p =

1D forms
2. Fluid-solid viscous interactions (Darcys
Law)

3. Conservation of mass

u
U =
(
v
f
v
s
)
= v
rel
v
s
=
t
4. Conservation of momentum
= 0
20.310, 2.793, 6.024
Fall, 2006
tot

11
= (2G + )
11
p
U
1
= k
p
x
1
U
1
=
u
1
+ U
0
t

11
= 0
x
1
2
u
1
u
1
= Hk
t x
1
25
Poroelasticity -- confined compression
Impose displacements at boundaries:
u
1
(x
1
, t=0) =0
11
u
1
(x
1
=L, t>0) =0
u
1
u
1
u
1
(x
1
=0, t>0) =u
0
2
u
1
u
1
x
1
= Hk
t x
1
Characteristic time ~L
2
/Hk
x
1
_

,
Solution (Fourier series)
t

t
u
1
(x
1
, t ) = u
0
1
x
1
A
n
sin
nr x
1
exp
L L
n n
_

,
L
2
=
n 2

2
Hk n
20.310, 2.793, 6.024
Fall, 2006

,
Finite rates of protein folding and unfolding can
also contribute to time-dependent behavior
AFM can be used to measure both
the elastic (k) and viscous (z)
properties of a single molecule as a

function of extension
Sequential unfolding of the
immunoglobulin (Ig) domains of titin
during oscillations to measure
viscoelasticity
Siingle molecule elastic and viscous
properties appear to scale with
each other
Kawakami et al., BJ, 2006
20.310, 2.793, 6.024
Fall, 2006
26
Figure by MIT OCW.
Extension (nm)
k

(
p
N
/
n
m
)
F
o
r
c
e

(
p
N
)

(
1
0
-
7

k
g
/
s
e
c
)
20
20
40
40
60 80 100
0
0
2
4
6
50
100
150
20.310, 2.793, 6.024
Fall, 2006
Additional factors: Ionic strength
+ 2G
27
Figure by MIT OCW.
1.2
1
0.8
0.6
0.4
0.2
0.001 0.01 0.1 1
Electrostatic: GAG
other
E
q
u
i
l
i
b
r
i
u
m

M
o
d
u
l
u
s
,

M
P
a
Ionic Strength, M
Equilibrium Modulus of Adult Bovine Articular Cartilage
in Different Ionic Strengths