TY - JOUR
T1 - Modeling cell migration regulated by cell extracellular-matrix micromechanical coupling
AU - Zheng, Yu
AU - Nan, Hanqing
AU - Liu, Yanping
AU - Fan, Qihui
AU - Wang, Xiaochen
AU - Liu, Ruchuan
AU - Liu, Liyu
AU - Ye, Fangfu
AU - Sun, Bo
AU - Jiao, Yang
N1 - Funding Information:
The authors are extremely grateful to the anonymous reviewers. Y.Z., H.N., and Y.J. thank Arizona State University for the generous startup funds and the University Graduate Fellowships. This work is partially supported by the National Science Foundation Grant No. CMMI-1916878. Q.F., X.W., and F.Y. thank the Chinese Academy of Sciences (CAS), the Key Research Program of Frontier Sciences of CAS (Grant No. QYZDB-SSW-SYS003). L.L. and R.L. thank the National Natural Science Foundation of China (Grants No. 11674043 and No. 11604030). B.S. thanks the Scialog Program for support sponsored jointly by Research Corporation for Science Advancement and the Gordon and Betty Moore Foundation. B.S. is partially supported by the Medical Research Foundation of Oregon and SciRIS-II award from Oregon State University and by the National Science Foundation Grant No. PHY-1400968.
Publisher Copyright:
© 2019 American Physical Society.
PY - 2019/10/11
Y1 - 2019/10/11
N2 - Cell migration in fibrous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response, and cancer progression. During migration, individual cells can generate active pulling forces via actomyosin contraction, which are transmitted to the ECM fibers through focal adhesion complexes, remodel the ECM, and eventually propagate to and can be sensed by other cells in the system. The microstructure and physical properties of the ECM can also significantly influence cell migration, e.g., via durotaxis and contact guidance. Here, we develop a computational model for two-dimensional cell migration regulated by cell-ECM micromechanical coupling. Our model explicitly takes into account a variety of cellular-level processes, including focal adhesion formation and disassembly, active traction force generation and cell locomotion due to actin filament contraction, transmission and propagation of tensile forces in the ECM, as well as the resulting ECM remodeling. We validate our model by accurately reproducing single-cell dynamics of MCF-10A breast cancer cells migrating on collagen gels and show that the durotaxis and contact guidance effects naturally arise as a consequence of the cell-ECM micromechanical interactions considered in the model. Moreover, our model predicts strongly correlated multicellular migration dynamics, which are resulted from the ECM-mediated mechanical coupling among the migrating cell and are subsequently verified in in vitro experiments using MCF-10A cells. Our computational model provides a robust tool to investigate emergent collective dynamics of multicellular systems in complex in vivo microenvironment and can be utilized to design in vitro microenvironments to guide collective behaviors and self-organization of cells.
AB - Cell migration in fibrous extracellular matrix (ECM) is crucial to many physiological and pathological processes such as tissue regeneration, immune response, and cancer progression. During migration, individual cells can generate active pulling forces via actomyosin contraction, which are transmitted to the ECM fibers through focal adhesion complexes, remodel the ECM, and eventually propagate to and can be sensed by other cells in the system. The microstructure and physical properties of the ECM can also significantly influence cell migration, e.g., via durotaxis and contact guidance. Here, we develop a computational model for two-dimensional cell migration regulated by cell-ECM micromechanical coupling. Our model explicitly takes into account a variety of cellular-level processes, including focal adhesion formation and disassembly, active traction force generation and cell locomotion due to actin filament contraction, transmission and propagation of tensile forces in the ECM, as well as the resulting ECM remodeling. We validate our model by accurately reproducing single-cell dynamics of MCF-10A breast cancer cells migrating on collagen gels and show that the durotaxis and contact guidance effects naturally arise as a consequence of the cell-ECM micromechanical interactions considered in the model. Moreover, our model predicts strongly correlated multicellular migration dynamics, which are resulted from the ECM-mediated mechanical coupling among the migrating cell and are subsequently verified in in vitro experiments using MCF-10A cells. Our computational model provides a robust tool to investigate emergent collective dynamics of multicellular systems in complex in vivo microenvironment and can be utilized to design in vitro microenvironments to guide collective behaviors and self-organization of cells.
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U2 - 10.1103/PhysRevE.100.043303
DO - 10.1103/PhysRevE.100.043303
M3 - Article
C2 - 31770879
AN - SCOPUS:85073833590
VL - 100
JO - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics
JF - Physical Review E - Statistical, Nonlinear, and Soft Matter Physics
SN - 1539-3755
IS - 4
M1 - 043303
ER -