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WIREs Syst Biol Med
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Modeling, signaling and cytoskeleton dynamics: integrated modeling‐experimental frameworks in cell migration

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Cell migration is a complex and multistep process involved in homeostasis maintenance, morphogenesis, and disease development, such as cancer metastasis. Modeling cell migration and the relevant cytoskeleton dynamics have profound implications for studying fundamental development and disease diagnosis. This review focuses on some recent models of both cell migration and migration‐related cytoskeleton dynamics, addressing issues such as the difference between amoeboid and mesenchymal migration modes, and between single‐cell migration and collective cell migration. The review also highlights the computational integration among variable external cues, especially the biochemical and mechanical signaling that affects cell migration. Finally, we aim to identify the gaps in our current knowledge and potential strategies to develop integrated modeling–experimental frameworks for multiscale behavior integrating gene expression, cell signaling, mechanics, and multicellular dynamics. WIREs Syst Biol Med 2017, 9:e1365. doi: 10.1002/wsbm.1365 This article is categorized under: Models of Systems Properties and Processes > Cellular Models Biological Mechanisms > Cell Signaling Analytical and Computational Methods > Computational Methods
Force balancing models of cell migration. (a) A force balancing model of individual cell migration. (b) The later experimental validation (left) is consistent with the computational predictions (right), which successfully predicted the cell migration speed dependence on both the integrin concentration and the matrix stiffness. (Reprinted with permission from Ref . Copyright 2006 National Academy of Sciences) (c) A force balancing model of collective monolayer cell migration. (d) This model successfully explained the mechanical wave‐like cell migration and stress patterns, which are due to the reinforcement and fluidization of cytoskeleton. The experimental measurement is on the left and the numerical simulation is on the right using the force balancing model. (Reprinted with permission from Ref . Copyright 2012 Macmillan Publishers Ltd)
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The integrated signaling pathway of N‐glycosylation, Wnt/β‐catenin, and E‐cadherin/β‐catenin. The signaling pathway map (a) that integrates model of N‐glycosylation, Wnt/β‐catenin, and E‐cadherin/β‐catenin represents how signaling molecules interact in a kinetic network. The quantitative predictions of the model (b: left) are validated in experiments of cell migration (b: right). (Reprinted with permission from Ref . Copyright 2016; https://creativecommons.org/licenses/by/4.0/)
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The signaling pathways of cytoskeleton dynamics in cell migration. Here is a signaling pathway map that represents how external cues regulate cytoskeleton dynamics, and further induce directional cell migration through these downstream signaling molecules. Several modeling work of these signaling pathways have been built upon these interactions and crosstalks, and they further predict or explain the integrated effects of signaling molecules in affecting cell migration.
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The vertex model and its potential force balancing correspondence. (a) The vertex model for collective cell migration in 2D and 3D, with the difference in cell–ECM contact area part and whether to include the elasticity of ECM matrix when cells invading into the matrix. (b) An appropriate analog between the energy‐based model and force balancing model is needed.
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Biological Mechanisms > Cell Signaling
Analytical and Computational Methods > Computational Methods
Models of Systems Properties and Processes > Cellular Models

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