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      Focal Adhesion–Independent Cell Migration

      1 , 2 , 1 , 2 , 3
      Annual Review of Cell and Developmental Biology
      Annual Reviews

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          Abstract

          Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion–independent migration, and highlight the remaining open questions for the future.

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          Most cited references118

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          Is Open Access

          Plasticity of cell migration: a multiscale tuning model

          Cell migration underlies tissue formation, maintenance, and regeneration as well as pathological conditions such as cancer invasion. Structural and molecular determinants of both tissue environment and cell behavior define whether cells migrate individually (through amoeboid or mesenchymal modes) or collectively. Using a multiparameter tuning model, we describe how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants—including cell–cell and cell–matrix adhesion, cytoskeletal polarity and stiffness, and pericellular proteolysis—interdependently control migration mode and efficiency. Motile cells integrate variable inputs to adjust interactions among themselves and with the matrix to dictate the migration mode. The tuning model provides a matrix of parameters that control cell movement as an adaptive and interconvertible process with relevance to different physiological and pathological contexts.
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            Life at low Reynolds number

            E. Purcell (1977)
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              Mechanical integration of actin and adhesion dynamics in cell migration.

              Directed cell migration is a physical process that requires dramatic changes in cell shape and adhesion to the extracellular matrix. For efficient movement, these processes must be spatiotemporally coordinated. To a large degree, the morphological changes and physical forces that occur during migration are generated by a dynamic filamentous actin (F-actin) cytoskeleton. Adhesion is regulated by dynamic assemblies of structural and signaling proteins that couple the F-actin cytoskeleton to the extracellular matrix. Here, we review current knowledge of the dynamic organization of the F-actin cytoskeleton in cell migration and the regulation of focal adhesion assembly and disassembly with an emphasis on how mechanical and biochemical signaling between these two systems regulate the coordination of physical processes in cell migration.
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                Author and article information

                Journal
                Annual Review of Cell and Developmental Biology
                Annu. Rev. Cell Dev. Biol.
                Annual Reviews
                1081-0706
                1530-8995
                October 06 2016
                October 06 2016
                : 32
                : 1
                : 469-490
                Affiliations
                [1 ]MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom WC1E 6BT;
                [2 ]Institute for the Physics of Living Systems, University College London, London, United Kingdom, WC1E 6BT
                [3 ]Institute of Science and Technology Austria (IST Austria), 3400 Klosterneuburg, Austria
                Article
                10.1146/annurev-cellbio-111315-125341
                27501447
                0f4d62f2-72f6-4ee1-bceb-1459f230170d
                © 2016
                History

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