Background: Collagen gels are important as platforms for in vitro study of cell behavior and as prototypical bioartificial tissues, but their mechanical behavior, particularly on the microscopic scale, is still poorly understood. Method of Approach: Collagen gels were studied in step (10% strain in 0.05 s) and ramp (0.1%/s strain rate for 100 s) confined compression. Real-time birefringence mapping gave the local collagen concentration and orientation along with piston stress. Variations in the retardation allowed material-point tracking and qualitative determination of the strain distribution. Results: Ramp tests showed classical poroelastic behavior: compression near the piston and relaxation to a uniform state. Step tests, however, showed an irreversibly collapsed region near the piston. Conclusions: Our results suggest that interstitial flow and fibril bending at crosslinks are the dominant mechanical processes during compression, and that fibril bending is reversible before collapse.

1.
Veis
,
A.
,
1982
, “
Collagen Fibrillogenesis
,”
Connect. Tissue Res.
,
10
, pp.
11
24
.
2.
Holmes
,
D. F.
,
Graham
,
H. K.
,
Trotter
,
J. A.
, and
Kadler
,
K. E.
,
2001
, “
STEM/TEM Studies of Collagen Fibril Assembly
,”
Micron
,
32
, pp.
273
85
.
3.
Kadler
,
K. E.
,
Holmes
,
D. F.
,
Graham
,
H.
, and
Starborg
,
T.
,
2000
, “
Tip-Mediated Fusion Involving Unipolar Collagen Fibrils Accounts for Rapid Fibril Elongation, the Occurrence of Fibrillar Branched Networks in Skin and the Paucity of Collagen Fibril Ends in Vertebrates
,”
Matrix Biol.
,
19
, pp.
359
65
.
4.
Kadler
,
K. E.
,
Holmes
,
D. F.
,
Trotter
,
J. A.
, and
Chapman
,
J. A.
,
1996
, “
Collagen Fibril Formation
,”
Biochem. J.
,
316
, pp.
1
11
.
5.
Tranquillo, R. T., 1999, “Self-Organization of Tissue-Equivalents: The Nature and Role of Contact Guidance,” Biochemical Society Symposia., 65, pp. 27–42.
6.
Allen
,
T. D.
,
Schor
,
S. L.
, and
Schor
,
A. M.
, 1984, “An Ultrastructural Review of Collagen Gels, a Model System for Cell-Matrix, Cell-Basement Membrane and Cell-Cell Interactions,” Scan Electron Microsc., 375–90.
7.
Roeder
,
B. A.
,
Kokini
,
K.
,
Surgis
,
J. E.
,
Robinson
,
J. P.
, and
Voytik-Harbin
,
S. L.
,
2002
, “
Tensile Mechanical Properties of Three-Dimensional Type I Collagen Extracellular Matrices with Varied Microstructure
,”
J. Biomech. Eng.
,
124
, pp.
214
223
.
8.
Grinnell
,
F.
, and
Lamke
,
C. R.
,
1984
, “
Reorganization of Hydrated Collagen Lattices by Human Skin Fibroblasts
,”
J. Cell. Sci.
,
66
, pp.
51
63
.
9.
Guidry
,
C.
, and
Grinnell
,
F.
,
1986
, “
Contraction of Hydrated Collagen Gels by Fibroblasts: Evidence of Two Mechanisms by Which Collagen Fibrils are Stabilized
,”
Coll. Relat. Res.
,
6
, pp.
515
529
.
10.
Bell, E., Ivarsson, B., and Merrill, C., 1979, “Production of a Tissue-Like Structure by Contraction of Collagen Lattices by Human Fibroblasts of Different Proliferative Potential In Vivo,” Proceedings of the National Academy of Sciences of the USA, 76, pp. 1274-8.
11.
Elsdale
,
T.
, and
Bard
,
J.
,
1972
, “
Collagen Substrata for Studies on Cell Behavior
,”
J. Cell Biol.
,
54
, pp.
626
37
.
12.
Stopak
,
D.
, and
Harris
,
A. K.
,
1982
, “
Connective Tissue Morphogenesis by Fibroblast Traction. I. Tissue Culture Observations
,”
Dev. Biol.
,
90
, pp.
383
98
.
13.
Auger
,
F. A.
,
Rouabhia
,
M.
,
Goulet
,
F.
,
Berthod
,
F.
,
Moulin
,
V.
, and
Germain
,
L.
,
1998
, “
Tissue-Engineered Human Skin Substitutes Developed from Collagen-Populated Hydrated Gels: Clinical and Fundamental Applications
,”
Med. Biol. Eng. Comput.
,
36
, pp.
801
812
.
14.
Wakatsuki
,
T.
,
Kolodney
,
M. S.
,
Zahalak
,
G. I.
, and
Elson
,
E. L.
,
2000
, “
Cell Mechanics Studied by a Reconstituted Model Tissue
,”
Biophys. J.
,
79
, pp.
2353
2368
.
15.
Grodzinsky
,
A. J.
,
Levenston
,
M. E.
,
Jin
,
M.
, and
Frank
,
E. H.
, 2000, “Cartilage Tissue Remodeling in Response to Mechanical Forces,” Annual Review of Biomedical Engineering, 2, pp. 691–713.
16.
Guilak
,
F.
, and
Mow
,
V. C.
,
2000
, “
The Mechanical Environment of the Chondrocyte: A Biphasic Finite Element Model of Cell-Matrix Interactions in Articular Cartilage
,”
J. Biomech.
,
33
, pp.
1663
73
.
17.
Mow
,
V. C.
,
Wang
,
C. C.
, and
Hung
,
C. T.
,
1999
, “
The Extracellular Matrix, Interstitial Fluid and Ions as a Mechanical Signal Transducer in Articular Cartilage
,”
Osteoarthritis Cartilage
,
7
, pp.
41
58
.
18.
Barocas
,
V. H.
,
Moon
,
A. G.
, and
Tranquillo
,
R. T.
,
1995
, “
The Fibroblast-Populated Microsphere Assay of Cell Traction Force—Part 2. Measurement of the Cell Traction Coefficient
,”
J. Biomech. Eng.
,
117
, pp.
161
170
.
19.
Parsons
,
J. W.
, and
Coger
,
R. N.
,
2002
, “
A New Device for Measuring the Viscoelastic Properties of Hydrated Matrix Gels
,”
J. Biomech. Eng.
,
124
, pp.
145
54
.
20.
Velegol
,
D.
, and
Lanni
,
F.
,
2001
, “
Cell Traction Forces on Soft Biomaterials. I. Microrheology of Type I Collagen Gels
,”
Biophys. J.
,
81
, pp.
1786
92
.
21.
Ferry, J. D., 1970, Viscoelastic Properties of Polymers, Wiley.
22.
Graessley, W. W., 1974, The Entanglement Concept in Polymer Rheology, Berlin; New York: Springer-Verlag.
23.
Tower
,
T. T.
,
Neidert
,
M. R.
, and
Tranquillo
,
R. T.
, “Fiber Alignment Imaging During Mechanical Testing of Soft Tissues,” Ann. Biomed. Eng., 30(10), pp. 1221–1233.
24.
Ozerdem
,
B.
, and
Tozeren
,
A.
,
1995
, “
Physical Response of Collagen Gels to Tensile Strain
,”
ASME J. Biomech. Eng.
,
117
, pp.
397
401
.
25.
Agoram
,
B.
, and
Barocas
,
V. H.
,
2001
, “
Coupled Macroscopic and Microscopic Scale Modeling of Fibrillar Tissues and Tissue Equivalents
,”
J. Biomech. Eng.
,
123
, pp.
362
9
.
26.
Voytik-Harbin
,
S. L.
,
Roeder
,
B. A.
,
Sturgis
,
J. E.
,
Kokini
,
K.
, and
Robinson
,
J. P.
,
2003
, “
Simultaneous Mechanical Loading and Confocal Reflection Microscopy for Three-Dimensional Microbiomechanical Analysis of Biomaterials and Tissue Constructs
,”
Microscopy and Microanalysis
,
9
, pp.
74
85
.
27.
Knapp
,
D. M.
,
Barocas
,
V. H.
,
Moon
,
A. G.
,
Yoo
,
K.
,
Petzold
,
L. R.
, and
Tranquillo
,
R. T.
,
1997
, “
Rheology of Reconstituted Type I Collagen Gel in Confined Compression
,”
J. Rheol.
,
41
, pp.
971
993
.
28.
Harrigan
,
T. P.
,
1987
, “
Cartilage is Poroelastic but not Biphasic
,”
J. Biomech.
,
20
, pp.
827
9
.
29.
Mow
,
V. C.
,
Kuei
,
S. C.
,
Lai
,
W. M.
, and
Armstrong
,
C. G.
,
1980
, “
Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression: Theory and Experiments
,”
J. Biomech. Eng.
,
102
, pp.
73
84
.
30.
Simon
,
B. R.
,
Coats
,
R. S.
, and
Woo
,
S. L.
,
1984
, “
Relaxation and Creep Quasilinear Viscoelastic Models for Normal Articular Cartilage
,”
J. Biomech. Eng.
,
106
, pp.
159
64
.
31.
Girton
,
T. S.
,
Barocas
,
V. H.
, and
Tranquillo
,
R. T.
,
2002
, “
Confined Compression of a Tissue-Equivalent: Collagen Fibril and Cell Alignment in Response to Anisotropic Strain
,”
J. Biomech. Eng.
,
124
,
568
575
.
32.
Barocas
,
V. H.
, and
Tranquillo
,
R. T.
,
1997
, “
An Anisotropic Biphasic Theory of Tissue-Equivalent Mechanics: The Interplay Among Cell Traction, Fibrillar Network Deformation, Fibril Alignment, and Cell Contact Guidance
,”
J. Biomech. Eng.
,
119
, pp.
137
145
.
33.
Dembo
,
M.
, and
Harlow
,
F.
,
1986
, “
Cell Motion, Contractile Networks, and the Physics of Interpenetrating Reactive Flow
,”
Biophys. J.
,
50
, pp.
109
121
.
34.
Armstrong
,
C. G.
,
Lai
,
W. M.
, and
Mow
,
V. C.
,
1984
, “
An Analysis of the Unconfined Compression of Articular Cartilage
,”
J. Biomech. Eng.
,
106
, pp.
165
173
.
35.
Tower
,
T. T.
, and
Tranquillo
,
R. T.
,
2001
, “
Alignment Maps in Tissues: II. Fast Harmonic Analysis for Imaging
,”
Biophys. J.
81
,
2964
297
.
36.
Wolman
,
M.
, and
Kasten
,
F. H.
,
1986
, “
Polarized Light Microscopy in the Study of the Molecular Structure of Collagen and Reticulin
,”
Histochemistry
,
85
, pp.
41
9
.
37.
Collett, E., 1993, Polarized Light: Fundamentals and Applications, Marcel Dekker, New York.
38.
Fuller, G. G., 1995, Optical Rheometry of Complex Fluids, Oxford University Press, New York.
39.
Roska
,
F. J.
, and
Ferry
,
J. D.
,
1982
, “
Studies of Fibrin Film. I. Stress Relaxation and Birefringence
,”
Biopolymers
,
21
, pp.
1811
32
.
40.
Chapuis
,
J. F.
,
LucarzBietry
,
A.
,
Agache
,
P.
, and
Humbert
,
P.
,
1996
, “
A Mechanical Study of Tense Collagen Lattices
,”
Eur. J. Dermatol.
,
6
, pp.
56
60
.
41.
Puxkandl
,
R.
and,
Zizak
,
I.
,
Paris
,
O.
,
Keckes
,
J.
,
Tesch
,
W.
,
Bernstorff
,
S.
,
Purslow
,
P.
, and
Fratzl
,
P.
,
2002
, “
Viscoelastic Properties of Collagen: Synchrotron Radiation Investigations and Structural Model
,”
Philosophical Transactions of the Royal Society of London–Series B: Biological Sciences.
,
357
(
1418
), pp.
191
197
.
42.
Moon, A. G., 1992, Ph.D. thesis in Chemical Engineering; Minneapolis, MN: University of Minnesota.
43.
Cheung
,
D. T.
, and
Nimri
,
M. E.
,
1982
, “
Mechanism of Crosslinking of Proteins by Glutaraldehyde II. Reaction with Monomeric and Polymeric Collagen
,”
Connect. Tissue Res.
,
10
(
2
), pp.
201
216
.
44.
Pineri
,
M. H.
,
Escoubes
,
M.
,
Roche
,
G.
,
1978
, “
Water-Collagen Interactions: Calorimetric and Mechanical Experiments
,”
Biopolymers
,
17
(
12
), pp.
2799
2815
.
45.
Traore
,
A.
,
Foucat
,
L.
,
Renou
,
J. P.
,
2000
, “
1H-nmr Study of Water Dynamics in Hydrated Collagen: Transverse Relaxation-Time and Diffusion Analysis
,”
Biopolymers
,
53
(
6
), pp.
476
483
.
46.
Christiansen
,
D. L.
,
Huang
,
E. K.
, and
Silver
,
F. H.
,
2000
, “
Assembly of Type I Collagen: Fusion of Fibril Subunits and the Influence of Fibril Diameter on Mechanical Properties
,”
Matrix Biol.
,
19
, pp.
409
420
.
47.
Hsu
,
S.
,
Jamieson
,
A. M.
, and
Blackwell
,
J.
,
1994
, “
Viscoelastic Studies of Extracellular Matrix Interactions in a Model Native Collagen Gel System
,”
Biorheology
,
31
, pp.
21
36
.
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