A method to impose and measure a one dimensional strain field via confined compression of a tissue-equivalent and measure the resulting cell and collagen fibril alignment was developed. Strain was determined locally by the displacement of polystyrene beads dispersed and entrapped within the network of collagen fibrils along with the cells, and it was correlated to the spatial variation of collagen network birefringence and concentration. Alignment of fibroblasts and smooth muscle cells was determined based on the long axis of elongated cells. Cell and collagen network alignment were observed normal to the direction of compression after a step strain and increased monotonically up to 50% strain. These results were independent of time after straining over 24 hr despite continued cell motility after responding instantly to the step strain with a change in alignment by deforming/convecting with the strained network. Since the time course of cell alignment followed that of strain and not stress which, due to the viscoelastic fluid-like nature of the network relaxes completely within the observation period, these results imply cell alignment in a compacting tissue-equivalent is due to fibril alignment associated with anisotropic network strain. Estimation of a contact guidance sensitivity parameter indicates that both cell types align to a greater extent than the surrounding fibrils.

1.
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
.
2.
Barocas, V. H. and Tranquillo, R. T., 1994, “Biphasic Theory and In Vitro Assays of Cell-fibril Mechanical Interactions in Tissue-equivalent Collagen Gels,” in Cell Mechanics and Cellular Engineering, V. C. Mow, et al., Editors, Springer-Verlag: New York. p. 185–209.
3.
Holmes
,
M. H.
,
1986
, “
Finite Deformation of Soft Tissue: Analysis of a Mixture Model in Uniaxial Compression
,”
J. Biomech. Eng.
,
108
, pp.
372
381
.
4.
Kwan
,
M. K.
,
Lai
,
W. M.
, and
Mow
,
V. C.
,
1990
, “
A Finite Deformation Theory for Cartilage and Other Soft Hydrated Connective Tissues–I. Equilibrium Results
,”
J. Biomech.
,
23
, pp.
145
155
.
5.
Setton
,
L. A.
,
Zhu
,
W.
, and
Mow
,
V. C.
,
1993
, “
The Biphasic Poroviscoelastic Behavior of Articular Cartilage: Role of the Surface Zone in Governing the Compressive Behavior
,”
J. Biomech.
,
26
, pp.
581
592
.
6.
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
.
7.
Eastwood
,
M.
,
Porter
,
R.
,
Khan
,
U.
,
McGrouther
,
G.
, and
Brown
,
R.
,
1996
, “
Quantitative Analysis of Collagen Gel Contractile Forces Generated by Dermal Fibroblasts and the Relationship to Cell Morphology
,”
J. Cell. Physiol.
,
166
, pp.
33
42
.
8.
Knapp
,
D. M.
,
Barocas
,
V. B.
,
Tower
,
T. T.
, and
Tranquillo
,
R. T.
,
1999
, “
Estimation of Cell Traction and Migration in an Isometric Cell Traction Assay
,”
AIChE J.
,
45
, pp.
2628
2640
.
9.
Barocas
,
V. H.
, and
Tranquillo
,
R. T.
,
1997
, “
A Finite Element Solution for the Anisotropic Biphasic Theory of Tissue-equivalent Mechanics: The Effect of Contact Guidance on Isometric Cell Traction Measurement
,”
J. Biomech. Eng.
,
119
, pp.
261
269
.
10.
Eastwood
,
M.
,
Mudera
,
V. C.
,
McGrouther
,
D. A.
, and
Brown
,
R. A.
,
1998
, “
Effect of Precise Mechanical Loading on Fibroblast Populated Collagen Lattices: Morphological Changes
,”
Cell Motil. Cytoskeleton
,
40
, pp.
13
21
.
11.
Guilak
,
F.
,
1995
, “
Compression-induced Changes in the Shape and Volume of the Chondrocyte Nucleus
,”
J. Biomech.
,
28
, pp.
1529
1541
.
12.
Buschmann
,
M. D.
,
Hunziker
,
E. B.
,
Kim
,
Y. J.
, and
Grodzinsky
,
A. J.
,
1996
, “
Altered Aggrecan Synthesis Correlates with Cell and Nucleus Structure in Statically Compressed Cartilage
,”
J. Cell. Sci.
,
109
, pp.
499
508
.
13.
Torzilli
,
P. A.
, et al.
,
1997
, “
Characterization of Cartilage Metabolic Response to Static and Dynamic Stress Using a Mechanical Explant Test System
,”
J. Biomech.
,
30
, pp.
1
9
.
14.
Chen
,
A. C.
, and
Sah
,
R. L.
,
1998
, “
Effect of Static Compression on Proteoglycan Biosynthesis by Chondrocytes Transplanted to Articular Cartilage In Vitro
,”
J. Orthop. Res.
,
16
, pp.
542
550
.
15.
Quinn
,
T. M.
,
Grodzinsky
,
A. J.
,
Buschmann
,
M. D.
,
Kim
,
Y. J.
, and
Hunziker
,
E. B.
,
1998
, “
Mechanical Compression Alters Proteoglycan Deposition and Matrix Deformation Around Individual Cells in Cartilage Explants
,”
J. Cell. Sci.
,
111
, pp.
573
583
.
16.
Valhmu
,
W. B.
, et al.
,
1998
, “
Load-controlled Compression of Articular Cartilage Induces a Transient Stimulation of Aggrecan Gene Expression
,”
Arch. Biochem. Biophys.
,
353
, pp.
29
36
.
17.
Tranquillo
,
R. T.
,
Girton
,
T. S.
,
Bromberek
,
B. A.
,
Triebes
,
T. G.
, and
Mooradian
,
D. L.
,
1996
, “
Magnetically-oriented Tissue-equivalent Tubes: Application to a Circumferentially-oriented Media-equivalent
,”
Biomaterials
,
17
, pp.
349
357
.
18.
Guido
,
S.
, and
Tranquillo
,
R. T.
,
1993
, “
A Methodology for the Systematic and Quantitative Study of Cell Contact Guidance in Oriented Collagen Gels: Correlation of Fibroblast Orientation and Gel Birefringence
,”
J. Cell. Sci.
,
105
, pp.
317
331
.
19.
Tower
,
T. T.
, and
Tranquillo
,
R. T.
,
2001
, “
Alignment Maps in Tissues and Fibrillar Materials: I. Microscopic Elliptical Polarimetry
,”
Biophys. J.
,
81
, pp.
2964
2971
.
20.
Bennett, H. S., “The Microscopical Investigation of Biological Materials with Polarized Light,” in McClung’s Handbook of Microscopical Technique, R. McClung-Jones, Editor. 1950, Paul B. Hoeber: New York. p. 591–677.
21.
Ortmann
,
R.
,
1975
, “
Use of Polarized Light for Quantitative Determination of the Adjustment of the Tangential Fibers in Articular Cartilage
,”
Anat. Embryol. (Berl)
,
148
, pp.
109
120
.
22.
Mardia, K. V., 1972, Statistics of Directional Data. Probability and Mathematical Statistics, ed. Z. W. Birnbaum and E. Lukacs. Vol. 13. Academic Press, London, p.
23.
Barocas
,
V. H.
,
Girton
,
T. S.
, and
Tranquillo
,
R. T.
,
1998
, “
Engineered Alignment in Media-equivalents: Magnetic Prealignment and Mandrel Compaction
,”
J. Biomech. Eng.
,
120
, pp.
660
666
.
24.
Tranquillo, R. T., “Self-organization of Tissue-equivalents: The Nature and Role of Contact Guidance,” in Cell Behaviour: Control and Mechanism of Motility, J. Lackie, G. Dunn, and G. Jones, Editors. 1998, Portland Press: Oxford. p. 27–42.
25.
Dubey, N., Letourneau, P. C., and Tranquillo, R. T., 2001, “Investigation of the Mechanism of Contact Guidance of Neutrite Growth Cones in Magnetically Aligned Collagen Gel,” in preparation.
26.
Ye
,
Q.
, et al.
,
2000
, “
Fibrin Gel as a Three Dimensional Matrix in Cardiovascular Tissue Engineering
,”
Eur. J. Cardiothorac Surg.
,
17
, pp.
587
591
.
27.
Grassl
,
E. D.
,
Oegema
,
T. R.
, and
Tranquillo
,
R. T.
,
2002
, “
Fibrin as an Alternative Biopolymer to Type I Collagen for Fabrication of a Media-equivalent
,”
J. Biomed. Mater. Res.
,
60
, pp.
607
612
.
28.
Neidert
,
M. R.
,
Lee
,
E. S.
,
Tower
,
T. T.
,
Oegema
,
T. R.
, and
Tranquillo
,
R. T.
,
2001
, “
Enhanced Fibrin Remodeling In Vitro with TGF-b1, Insulin and Plasmin for Improved Tissue-equivalents
,”
Biomaterials
,
23
, pp.
3717
3731
.
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