We have recently demonstrated that the mitral valve anterior leaflet (MVAL) exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315–325;Grashow et al., 2006, Ann Biomed. Eng., 34(10), pp. 1509–1518). However, the underlying structural basis for this unique quasi-elastic mechanical behavior is presently unknown. As collagen is the major structural component of the MVAL, we investigated the relation between collagen fibril kinematics (rotation and stretch) and tissue-level mechanical properties in the MVAL under biaxial loading using small angle X-ray scattering. A novel device was developed and utilized to perform simultaneous measurements of tissue level forces and strain under a planar biaxial loading state. Collagen fibril D-period strain (εD) and the fibrillar angular distribution were measured under equibiaxial tension, creep, and stress relaxation to a peak tension of 90Nm. Results indicated that, under equibiaxial tension, collagen fibril straining did not initiate until the end of the nonlinear region of the tissue-level stress-strain curve. At higher tissue tension levels, εD increased linearly with increasing tension. Changes in the angular distribution of the collagen fibrils mainly occurred in the tissue toe region. Using εD, the tangent modulus of collagen fibrils was estimated to be 95.5±25.5MPa, which was 27 times higher than the tissue tensile tangent modulus of 3.58±1.83MPa. In creep tests performed at 90Nm equibiaxial tension for 60min, both tissue strain and εD remained constant with no observable changes over the test length. In contrast, in stress relaxation tests performed for 90minεD was found to rapidly decrease in the first 10min followed by a slower decay rate for the remainder of the test. Using a single exponential model, the time constant for the reduction in collagen fibril strain was 8.3min, which was smaller than the tissue-level stress relaxation time constants of 22.0 and 16.9min in the circumferential and radial directions, respectively. Moreover, there was no change in the fibril angular distribution under both creep and stress relaxation over the test period. Our results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic viscoelastic behavior, (2) tissue relaxation results from the removal of stress from the fibrils, possibly by a slipping mechanism modulated by noncollagenous components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of stress relaxation suggests a “load-locking” behavior under maintained loading conditions. These unique mechanical characteristics are likely necessary for normal valvular function.

1.
Ranganathan
,
N.
,
Lam
,
J. H.
,
Wigle
,
E. D.
, and
Silver
,
M. D.
, 1970, “
Morphology of the Human Mitral Valve. II. The Value Leaflets
,”
Circulation
0009-7322
41
(
3
), pp.
459
467
.
2.
Sacks
,
M. S.
,
He
,
Z.
,
Baijens
,
L.
,
Wanant
,
S.
,
Shah
,
P.
,
Sugimoto
,
H.
, and
Yoganathan
,
A. P.
, 2000, “
Surface Strains in the Anterior Leaflet of the Functioning Mitral Valve
,”
Ann. Biomed. Eng.
0090-6964
30
(
10
), pp.
1281
1290
.
3.
He
,
Z.
,
Sacks
,
M. S.
,
Baijens
,
L.
,
Wanant
,
S.
,
Shah
,
P.
, and
Yoganathan
,
A. P.
, 2003, “
Effects of Papillary Muscle Position on In-Vitro Dynamic Strain on the Porcine Mitral Valve
,”
J. Heart Valve Dis.
0966-8519
12
(
4
), pp.
488
494
.
4.
Sacks
,
M. S.
,
Enomoto
,
Y.
,
Graybill
,
J. R.
,
Merryman
,
W. D.
,
Zeeshan
,
A.
,
Yoganathan
,
A. P.
,
Levy
,
R. J.
,
Gorman
,
R. C.
, and
Gorman
,
J. H.
, 2006, “
In-Vivo Dynamic Deformation of the Mitral Valve Anterior Leaflet
,”
Ann. Thorac. Surg.
0003-4975,
82
(
4
), pp.
1369
1377
.
5.
May-Newman
,
K.
, and
Yin
,
F. C.
, 1995, “
Biaxial Mechanical Behavior of Excised Porcine Mitral Valve Leaflets
,”
Am. J. Physiol.
0002-9513
269
(
4
Pt. 2), pp.
H1319
H1327
.
6.
May-Newman
,
K.
, and
Yin
,
F. C.
, 1998, “
A Constitutive Law for Mitral Valve Tissue
,”
ASME J. Biomech. Eng.
0148-0731
120
(
1
), pp.
38
47
.
7.
Grashow
,
J. S.
,
Yoganathan
,
A. P.
, and
Sacks
,
M. S.
, 2006, “
Biaxial Stress-Stretch Behavior of the Mitral Valve Anterior Leaflet at Physiologic Strain Rates
,”
Ann. Biomed. Eng.
0090-6964
34
(
2
), pp.
315
325
.
8.
Grashow
,
J. S.
,
Sacks
,
M. S.
,
Liao
,
J.
, and
Yoganathan
,
A. P.
, 2006, “
Planar Biaxial Creep and Stress Relaxation of the Mitral Valve Anterior Leaflet
,”
Ann. Biomed. Eng.
0090-6964,
34
(
10
), pp.
1509
1518
.
9.
Lis
,
Y.
,
Burleigh
,
M. C.
,
Parker
,
D. J.
,
Child
,
A. H.
,
Hogg
,
J.
, and
Davies
,
M. J.
, 1987, “
Biochemical Characterization of Individual Normal, Floppy and Rheumatic Human Mitral Valves
,”
Biochem. J.
0264-6021
244
(
3
), pp.
597
603
.
10.
Kunzelman
,
K. S.
,
Quick
,
D. W.
, and
Cochran
,
R. P.
, 1998, “
Altered Collagen Concentration in Mitral Valve Leaflets: Biochemical and Finite Element Analysis
,”
Ann. Thorac. Surg.
0003-4975
66
(
6
Suppl), pp.
S198
S205
.
11.
Silverman
,
M. E.
, and
Hurst
,
J. W.
, 1968, “
The Mitral Complex. Interaction of the Anatomy, Physiology, and Pathology of the Mitral Annulus, Mitral Valve Leaflets, Chordae Tendineae, and Papillary Muscles
,”
Am. Heart J.
0002-8703
76
(
3
), pp.
399
418
.
12.
Kunzelman
,
K. S.
,
Cochran
,
R. P.
,
Murphree
,
S. S.
,
Ring
,
W. S.
,
Verrier
,
E. D.
, and
Eberhart
,
R. C.
, 1993, “
Differential Collagen Distribution in the Mitral Valve and Its Influence on Biomechanical Behaviour
,”
J. Heart Valve Dis.
0966-8519
2
(
2
), pp.
236
244
.
13.
Billiar
,
K. L.
, and
Sacks
,
M. S.
, 1997, “
A Method to Quantify the Fiber Kinematics of Planar Tissues Under Biaxial Stretch
,”
J. Biomech.
0021-9290
30
(
7
), pp.
753
756
.
14.
Billiar
,
K. L.
, and
Sacks
,
M. S.
, 2000a, “
Biaxial Mechanical Properties of the Natural and Glutaraldehyde Treated Aortic Valve Cusp—Part I: Experimental Results
,”
ASME J. Biomech. Eng.
0148-0731
122
(
1
), pp.
23
30
.
15.
Billiar
,
K. L.
, and
Sacks
,
M. S.
, 2000b, “
Biaxial Mechanical Properties of the Native and Glutaraldehyde-Treated Aortic Valve Cusp: Part II—A Structural Constitutive Model
,”
ASME J. Biomech. Eng.
0148-0731
122
(
4
), pp.
327
335
.
16.
Grande-Allen
,
K. J.
,
Griffin
,
B. P.
,
Calabro
,
A.
,
Ratliff
,
N. B.
,
Cosgrove
III,
D. M.
, and
Vesely
,
I.
, 2001, “
Myxomatous Mitral Valve Chordae. II: Selective Elevation of Glycosaminoglycan Content
,”
J. Heart Valve Dis.
0966-8519
10
(
3
), pp.
325
332
, discussion 332–333.
17.
Elliott
,
D. M.
,
Robinson
,
P. S.
,
Gimbel
,
J. A.
,
Sarver
,
J. J.
,
Abboud
,
J. A.
,
Iozzo
,
R. V.
, and
Soslowsky
,
L. J.
, 2003, “
Effect of Altered Matrix Proteins on Quasilinear Viscoelastic Properties in Transgenic Mouse Tail Tendons
,”
Ann. Biomed. Eng.
0090-6964
31
(
5
), pp.
599
605
.
18.
Cavalcante
,
F. S.
,
Ito
,
S.
,
Brewer
,
K.
,
Sakai
,
H.
,
Alencar
,
A. M.
,
Almeida
,
M. P.
,
Andrade
Jr.,
J. S.
,
Majumdar
,
A.
,
Ingenito
,
E. P.
, and
Suki
,
B.
, 2005, “
Mechanical Interactions Between Collagen and Proteoglycans: Implications for the Stability of Lung Tissue
,”
J. Appl. Physiol.
8750-7587
98
(
2
), pp.
672
679
.
19.
Nimni
,
M. E.
, 1980 “
The Molecular Organization of Collgen and Its Role in Determining the Biophysical Properties of the Connective Tissues
,”
Biorheology
0006-355X
17
, pp.
51
82
.
20.
Fung
,
Y. C.
, 1993,
Biomechanics: Mechanical Properties of Living Tissues
,
2nd ed.
,
Springer
,
New York
, p.
568
.
21.
Silver
,
F. H.
,
Freeman
,
J. W.
, and
Seehra
,
G. P.
, 2003, “
Collagen Self-Assembly and the Development of Tendon Mechanical Properties
,”
J. Biomech.
0021-9290
36
(
10
), pp.
1529
1553
.
22.
Chapman
,
J. A.
, and
Hulmes
,
D. J. S.
, 1984, “
Electron Microscopy of the Collagen Fibril
,” in
Ultrastructure of the Connective Tissue Matrix
,
A.
Ruggeri
, and
P. M.
Motto
, eds.,
Martinus Nijhoff
,
Boston
, pp.
1
33
.
23.
Hodge
,
A. J.
, and
Petruska
,
J. A.
, 1963,
Recent Studies With the Electron Microscope on Ordered Aggregates of the Tropocollagen Molecule
,
Aspects of Protein Chemistry
Vol.
289–300
,
Academic
,
London
.
24.
Trotter
,
J. A.
, and
Koob
,
T. J.
, 1989, “
Collagen and Proteoglycan in a Sea Urchin Ligament With Mutable Mechanical Properties
,”
Cell Tissue Res.
0302-766X
258
(
3
), pp.
527
539
.
25.
Trotter
,
J. A.
,
Thurmond
,
F. A.
, and
Koob
,
T. J.
, 1994, “
Molecular Structure and Functional Morphology of Echinoderm Collagen Fibrils
,”
Cell Tissue Res.
0302-766X
275
(
3
), pp.
451
458
.
26.
Scott
,
J. E.
, 1991, “
Proteoglycan: Collagen Interactions in Connective Tissues. Ultrastructural, Biochemical, Functional and Evolutionary Aspects
,”
Int. J. Biol. Macromol.
0141-8130
13
(
3
), pp.
157
161
.
27.
Weber
,
I. T.
,
Harrison
,
R. W.
, and
Iozzo
,
R. V.
, 1996, “
Model Structure of Decorin and Implications for Collagen Fibrillogenesis
,”
J. Biol. Chem.
0021-9258
271
(
50
), pp.
31767
31770
.
28.
Kastelic
,
J.
,
Galeski
,
A.
, and
Baer
,
E.
, 1978, “
The Multicomposite Structure of Tendon
,”
Connect. Tissue Res.
0300-8207
6
(
1
), pp.
11
23
.
29.
Silver
,
F. H.
, 1987,
Biological Materials: Structure, Mechanical Properties, and Modeling of Soft Tissues
,
New York University Press
,
New York
.
30.
Hilbert
,
S. L.
,
Sword
,
L. C.
,
Batchelder
,
K. F.
,
Barrick
,
M. K.
, and
Ferrans
,
V. J.
, 1996, “
Simultaneous Assessment of Bioprosthetic Heart Valve Biomechanical Properties and Collagen Crimp Length
,”
J. Biomed. Mater. Res.
0021-9304
31
(
4
), pp.
503
509
.
31.
Hansen
,
K. A.
,
Weiss
,
J. A.
, and
Barton
,
J. K.
, 2002, “
Recruitment of Tendon Crimp With Applied Tensile Strain
,”
ASME J. Biomech. Eng.
0148-0731
124
(
1
), pp.
72
77
.
32.
Kronick
,
P. L.
, and
Buechler
,
P. R.
, 1986, “
Fiber Orientation in Calfskin by Laser Light Scattering or X-Ray Diffraction and Quantitative Relation to Mechanical Properties
,”
J. Am. Leather Chem. Ass.
,
81
, pp.
221
229
.
33.
Sacks
,
M. S.
,
Smith
,
D. B.
, and
Hiester
,
E. D.
, 1997, “
A Small Angle Light Scattering Device for Planar Connective Tissue Microstructural Analysis
,”
Ann. Biomed. Eng.
0090-6964
25
(
4
), pp.
678
689
.
34.
Farkasjahnke
,
M.
, and
S.
,
V.
, 1965, “
Small-Angle X-Ray Diffraction Studies on Rat-Tail Tendon
,”
Acta Physiol. Acad. Sci. Hung.
0001-6756
28
(
1
), pp.
1
17
.
35.
Bigi
,
A.
,
Incerti
,
A.
,
Leonardi
,
L.
,
Miccoli
,
G.
,
Re
,
G.
, and
Roveri
,
N.
, 1980, “
Role of the Orientation of the Collagen Fibers on the Mechanical Properties of the Carotid Wall
,”
Boll Soc. Ital. Biol. Sper
0037-8771
56
(
4
), pp.
380
384
.
36.
Aspden
,
R. M.
,
Bornstein
,
N. H.
, and
Hukins
,
D. W.
, 1987, “
Collagen Organisation in the Interspinous Ligament and Its Relationship to Tissue Function
,”
J. Anat.
0021-8782
155
, pp.
141
151
.
37.
Sasaki
,
N.
, and
Odajima
,
S.
, 1996, “
Stress-Strain Curve and Young’s Modulus of a Collagen Molecule as Determined by the X-Ray Diffraction Technique
,”
J. Biomech.
0021-9290
29
, pp.
655
658
.
38.
Folkhard
,
W.
,
Geercken
,
W.
,
Knorzer
,
E.
,
Mosler
,
E.
,
Nemetschek-Gansler
,
H.
,
Nemetschek
,
T.
, and
Koch
,
M. H.
, 1987, “
Structural Dynamic of Native Tendon Collagen
,”
J. Mol. Biol.
0022-2836
193
(
2
), pp.
405
407
.
39.
Fratzl
,
P.
,
Misof
,
K.
,
Zizak
,
I.
,
Rapp
,
G.
,
Amenitsch
,
H.
, and
Bernstorff
,
S.
, 1998, “
Fibrillar Structure and Mechanical Properties of Collagen
,”
J. Struct. Biol.
1047-8477
122
(
1–2
), pp.
119
122
.
40.
Sasaki
,
N.
, and
Odajima
,
S.
, 1996, “
Elongation Mechanism of Collagen Fibrils and Force-Strain Relations of Tendon at Each Level of Structural Hierarchy
,”
J. Biomech.
0021-9290
29
(
9
), pp.
1131
1136
.
41.
Sasaki
,
N.
,
Shukunami
,
N.
,
Matsushima
,
N.
, and
Izumi
,
Y.
, 1999, “
Time Resolved X-Ray Diffraction From Tendon Collagen During Creep Using Synchrotron Radiation
,”
J. Biomech.
0021-9290
32
, pp.
285
292
.
42.
Purslow
,
P. P.
,
Wess
,
T. J.
, and
Hukins
,
D. W.
, 1998, “
Collagen Orientation and Molecular Spacing During Creep and Stress-Relaxation in Soft Connective Tissues
,”
J. Exp. Biol.
0022-0949
201(Pt 1)
, pp.
135
142
.
43.
Gilbert
,
T. W.
,
Sacks
,
M. S.
,
Grashow
,
J. S.
,
Woo
,
S. L. Y.
,
Chancellor
,
M. B.
, and
Badylak
,
S. F.
, “
Fiber Kinematics of Small Intestinal Submucosa Under Uniaxial and Biaxial Stretch
,”
J. Biomech. Eng.
0148-0731 in press.
44.
Purslow
,
P. P.
,
Bigi
,
A.
,
Ripamonti
,
A.
, and
Roveri
,
N.
, 1984, “
Collagen Fibre Reorientation Around a Crack in Biaxially Stretched Materials
,”
Macromolecules
0024-9297
6
, pp.
21
25
.
45.
Liao
,
J.
,
Yang
,
L.
,
Grashow
,
J.
, and
Sacks
,
M. S.
, 2005, “
Molecular Orientation of Collagen in Intact Planar Connective Tissues Under Biaxial Stretch
,”
Acta Biomaterialia
,
1
(
1
), pp.
45
54
.
46.
Sacks
,
M. S.
, 2000, “
Biaxial Mechanical Evaluation of Planar Biological Materials
,”
J. Biomech.
0021-9290
61
, pp.
199
246
.
47.
Woo
,
S.
,
Orland
,
C. A.
,
Camp
,
J. F.
, and
Akeson
,
W. H.
, 1994, “
Effects of Postmortem Storage by Freezing on Ligament Tensile Behavior
,”
J. Biomech.
0021-9290
19
, pp.
399
404
.
48.
Spencer
,
A. J. M.
, 1980,
Continuum Mechanics
,
Longman Scientific & Technical
,
New York
, p.
183
.
49.
Liao
,
J.
, and
Vesely
,
I.
, 2003, “
A Structural Basis for the Size-Related Mechanical Properties of Mitral Valve Chordae Tendineae
,”
J. Biomech.
0021-9290
36
(
8
), pp.
1125
1133
.
50.
Kongsgaard
,
M.
,
Aagaard
,
P.
,
Kjaer
,
M.
, and
Magnusson
,
S. P.
, 2005, “
Structural Achilles Tendon Properties in Athletes Subjected to Different Exercise Modes and in Achilles Tendon Rupture Patients
,”
J. Appl. Physiol.
8750-7587
99
(
5
), pp.
1965
1971
.
51.
Thornton
,
G. M.
,
Oliynyk
,
A.
,
Frank
,
C. B.
, and
Shrive
,
N. G.
, 1997, “
Ligament Creep Cannot be Predicted From Stress Relaxation at Low Stress: A Biomechanical Study of the Rabbit Medial Collateral Ligament
,”
J. Orthop. Res.
0736-0266
15
(
5
), pp.
652
656
.
52.
Thornton
,
G. M.
,
Frank
,
C. B.
, and
Shrive
,
N. G.
, 2001, “
Ligament Creep Behavior Can Be Predicted From Stress Relaxation by Incorporating Fiber Recruitment
,”
J. Rheol.
0148-6055
45
(
2
), pp.
493
507
.
You do not currently have access to this content.