Abstract

Technical challenges, including significant ones associated with cell rearrangement, have hampered the development of three-dimensional finite element models for the mechanics of embryonic cells. These challenges have been overcome by a new formulation in which the contents of each cell, assumed to have a viscosity μ, are modeled using a system of orthogonal dashpots. This approach overcomes a stiffening artifact that affects more traditional models, in which space-filling viscous elements are used to model the cytoplasm. Cells are assumed to be polyhedral in geometry, and each n-sided polygonal face is subdivided into n triangles with a common node at the face center so that it needs not remain flat. A constant tension γ is assumed to act along each cell-cell interface, and cell rearrangements occur through one of two complementary topological transformations. The formulation predicts mechanical interactions between pairs of similar or dissimilar cells that are consistent with experiments, two-dimensional simulations, contact angle theory, and intracellular pressure calculations. Simulations of the partial engulfment of one tissue type by another show that the formulation is able to model aggregates of several hundred cells without difficulty. Simulations carried out using this formulation suggest new experimental approaches for measuring cell surface tensions and interfacial tensions. The formulation holds promise as a tool for gaining insight into the mechanics of isolated or aggregated embryonic cells and for the design and interpretation of experiments that involve them.

References

1.
Louzoun
,
Y.
,
Solomon
,
S.
,
Atlan
,
H.
, and
Cohen
,
I. R.
, 2001, “
Modeling Complexity in Biology
,”
Physica A
0378-4371,
297
(
1–2
), pp.
242
252
.
2.
Csete
,
M. E.
, and
Doyle
,
J. C.
, 2002, “
Reverse Engineering of Biological Complexity
,”
Science
0036-8075,
295
, pp.
1664
1669
.
3.
Honda
,
H.
, 1978, “
Description of Cellular Patterns by Dirichlet Domains: The Two-Dimensional Case
,”
J. Theor. Biol.
0022-5193,
72
, pp.
523
543
.
4.
Honda
,
H.
, 1983, “
Geometrical Models for Cells in Tissues
,”
Int. Rev. Cytol.
0074-7696,
81
, pp.
191
248
.
5.
Glazier
,
J. A.
, and
Graner
,
F.
, 1992, “
Simulation of Biological Cell Sorting Using a Two-Dimensional Extended Potts Model
,”
Phys. Rev. Lett.
0031-9007,
69
(
13
), pp.
2013
2016
.
6.
Glazier
,
J. A.
, and
Graner
,
F.
, 1993, “
Simulation of the Differential Adhesion Driven Rearrangement of Biological Cells
,”
Phys. Rev. E
1063-651X,
47
(
3
), pp.
2128
2154
.
7.
Clem
,
C. J.
,
Konig
,
D.
, and
Rigaut
,
J. P.
, 1997, “
A Three-dimensional Dynamic Simulation Model of Epithelial Tissue Renewal
,”
Anal Quant Cytol. Histol.
0884-6812,
19
, pp.
174
184
.
8.
Brodland
,
G. W.
, and
Chen
,
H. H.
, 2000, “
The Mechanics of Cell Sorting and Envelopment
,”
J. Biomech.
0021-9290,
33
, pp.
845
851
.
9.
Palsson
,
E.
, 2001, “
A Three-dimensional Model of Cell Movement in Multicellular Systems
,”
FGCS, Future Gener. Comput. Syst.
0167-739X,
17
, pp.
835
853
.
10.
Brodland
,
G. W.
, 2002, “
The Differential Interfacial Tension Hypothesis DITH: A Comprehensive Theory for the Self-Rearrangement of Embryonic Cells and Tissues
,”
ASME J. Biomech. Eng.
0148-0731,
124
, pp.
188
197
.
11.
Honda
,
H.
,
Tanemura
,
M.
, and
Nagai
,
T.
, 2003, “
A Three-Dimensional Vertex Dynamics Cell Model of Space-Filling Polyhedra Simulating Cell Behavior in a Cell Aggregate
,”
J. Theor. Biol.
0022-5193,
226
, pp.
439
453
.
12.
McGarry
,
J. G.
, and
Prendergast
,
P. J.
, 2004, “
A Three-dimensional Finite Element Model of an Adherent Eukaryotic Cell
,”
Eur. Cells Mater
1473-2262,
7
, pp.
27
34
.
13.
Brodland
,
G. W.
, 2004, “
Computational Modeling of Cell Sorting, Tissue Engulfment, and Related Phenomena: A Review
,”
Appl. Mech. Rev.
0003-6900,
57
(
1
), pp.
47
76
.
14.
Brodland
,
G. W.
, 2003, “
New Information from Cell Aggregate Compression Tests and its Implications for Theories of Cell Sorting
,”
Biorheology
0006-355X,
40
, pp.
273
277
.
15.
Lewis
,
F. T.
, 1923, “
The Typical Shape of Polyhedral Cells in Vege-Table Parenchyma and the Restoration of That Shape Following Cell Division
,”
Proc. Am. Acad. Arts Sci.
0065-6836,
58
(
15
), pp.
235
265
.
16.
Lewis
,
F. T.
, 1931, “
A Comparison Between the Mosaic of Polygons in a Film or Artificial Emulsion and the Pattern of Simple Epithelium in Surface View (Cucumber Epidermis and Human Amnion)
,”
Anat. Rec.
0003-276X,
50
, pp.
235
265
.
17.
Fuchizaki
,
K.
,
Kusaba
,
T.
, and
Kawasaki
,
K.
, 1995, “
Computer Modeling of Three-Dimensional Cellular Pattern Growth
,”
Philos. Mag. B
1364-2812,
71
, pp.
333
357
.
18.
Brodland
,
G. W.
, and
Wiebe
,
C. J.
, 2004, “
Mechanical Effects of Cell Anisotropy on Epithelia
,”
Comput. Methods Biomech. Biomed. Eng.
1025-5842,
7
(
2
), pp.
91
99
.
19.
Alberts
,
B.
, 2004,
Essential Cell Biology: An Introduction to the Molecular Biology of the Cell
, 2nd ed.,
Garland Science
,
New York
.
20.
Irons
,
B.
, and
Ahmad
,
S.
, 1986,
Techniques of Finite Elements
,
Ellis Horwood Limited/Wiley
,
Toronto
.
21.
Zienkiewicz
,
O. C.
, 1977,
The Finite Element Method
,
McGraw-Hill
,
London
.
22.
Brodland
,
G. W.
,
Viens
,
D.
, and
Veldhuis
,
J. H.
, 2007, “
A New Cell-Based FE Model for the Mechanics of Embryonic Epithelia
,”
Comput. Methods Biomech. Biomed. Eng.
1025-5842,
10
, pp.
121
128
.
23.
Davies
,
J.
, and
Rideal
,
E.
, 1963,
Interfacial Phenomena
,
Academic
,
New York
.
24.
Chen
,
H. H.
, and
Brodland
,
G. W.
, 2000, “
Cell-Level Finite Element Studies of Viscous Cells in Planar Aggregates
,”
ASME J. Biomech. Eng.
0148-0731,
122
, pp.
394
401
.
25.
Barber
,
C. B.
,
Dobkin
,
D. P.
, and
Huhdanpaa
,
H. T.
, 1996, “
The Quickhull Algorithm for Convex Hulls
,”
ACM Trans. Math. Softw.
0098-3500,
22
(
4
), pp.
469
483
.
26.
Brodland
,
G. W.
, and
Veldhuis
,
J. H.
, 2003, “
A Computer Model for Reshaping of Cells in Epithelia Due to In-Plane Deformation and Annealing
,”
Comput. Methods Biomech. Biomed. Eng.
1025-5842,
6
, pp.
89
98
.
27.
Miller
,
K.
, 2005, “
Method of Testing Very Soft Biological Tissues in Compression
,”
J. Biomech.
0021-9290,
38
, pp.
153
158
.
28.
Brodland
,
G. W.
,
Chen
,
D.
, and
Veldhuis
,
J. H.
, 2006, “
A Cell-Based Constitutive Model for Embryonic Epithelia and Other Planar Aggregates of Biological Cells
,”
Int. J. Plast.
0749-6419,
22
, pp.
965
995
.
29.
Steinberg
,
M. S.
, 1963, “
Reconstruction of Tissues by Dissociated Cells
,”
Science
0036-8075,
141
, pp.
401
408
.
30.
Flugge
,
W.
, 1973,
Stresses in Shells
, 2nd ed.,
Springer-Verlag
,
Berlin
.
31.
Gordon
,
R.
,
Goel
,
N. S.
,
Steinberg
,
M. S.
, and
Wiseman
,
L. L.
, 1975, “
A Rheological Mechanism Sufficient to Explain the Kinetics of Cell Sorting
,”
Mathematical Models for Cell Rearrangement
,
G. D.
Mostow
, ed.,
Yale University Press
,
New Haven
;
Gordon
,
R.
,
Goel
,
N. S.
,
Steinberg
,
M. S.
, and
Wiseman
,
L. L.
, 1972,
J. Theor. Biol.
0022-5193
37
, pp.
43
73
, reprinted from 1972.
32.
Armstrong
,
P. B.
, 1989, “
Cell Sorting Out: The Self-Assembly of Tissues In Vitro
,”
Crit. Rev. Biochem. Mol. Biol.
1040-9238,
24
(
2
), pp.
119
149
.
33.
Fricke
,
W.
, 2000, “
Water Movement Between Epidermal Cells of Barley Leaves—A Symplastic Connection?
,”
Plant, Cell Environ.
0140-7791,
23
, pp.
991
997
.
34.
Marcel
,
Y.
,
Avila
,
D. A.
,
Carré
,
R. A. S.
, and
Mortimer
,
M. C.
, 2001, “
Reliable Measurement of Mouse Intraocular Pressure by a Servo-Null Micropipette System
,”
Invest. Ophthalmol. Visual Sci.
0146-0404,
42
, pp.
1841
1846
.
35.
Foty
,
R. A.
,
Pfleger
,
C. M.
,
Forgacs
,
G.
, and
Steinberg
,
M. S.
, 1996, “
Surface Tensions of Embryonic Tissues Predict Their Mutual Envelopment Behavior
,”
Development
0950-1991,
122
(
5
), pp.
1611
1620
.
You do not currently have access to this content.