A three-dimensional computational model of collagen network mechanics.
Extracellular matrix (ECM) strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell-ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model) and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned). We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions.
Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia, United States of America.
Byoungkoo
B
Lee
School of Physics, Graduate University of Chinese Academy of Science, Beijing, China.
Xin
X
Zhou
Laboratory for Optical and Computational Instrumentation, Laboratory for Cell and Molecular Biology and Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Kristin
K
Riching
Laboratory for Optical and Computational Instrumentation, Laboratory for Cell and Molecular Biology and Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Kevin W
KW
Eliceiri
Laboratory for Optical and Computational Instrumentation, Laboratory for Cell and Molecular Biology and Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Patricia J
PJ
Keely
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, United States of America.
Scott A
SA
Guelcher
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Alissa M
AM
Weaver
Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia, United States of America.
Yi
Y
Jiang
D003094:Collagen / Q000378:metabolism*; D003198:Computer Simulation; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D013314:Stress, Mechanical; D013718:Tensile Strength
D003094:Collagen