Abstract
Studies of cell migration in three-dimensional (3D) cell culture systems and in vivo have revealed several differences when compared with cell migration in two dimensions, including their morphology and mechanical and signalling control. Here, researchers assess the contribution of 3D models to our understanding of cell migration, both in terms of the mechanisms used to drive single cell and collective cell migration and how migrating cells respond to a changing environment in vivo.
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Acknowledgements
P.F is supported by the Dutch Cancer Foundation (KWF 2008-4031) and the Netherlands Science Foundation (NWO-VICI 918.11.626). E.S. thanks Cancer Research UK for funding. K.M.Y. is supported by the Intramural Research Program of the NIDCR, NIH.
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Glossary
- β1 integrin
-
A cell surface, transmembrane protein that forms a heterodimer with distinct α-chains to generate adhesive structures that are capable of binding to subsets of extracellular matrix macromolecules (for example, type I collagen).
- Blebs
-
Rounded protrusions driven by hydrostatic pressure. Blebs initially lack filamentous actin (F-actin) and later incoporate cortical F-actin.
- Elastic modulus
-
The amount of force per unit area required to deform a material by a defined amount.
- Fibrillogenesis
-
The formation of fibrillar arrays of extracellular matrix molecules by head-to-head and side-to-side interactions between protomer subunits.
- Filopodia
-
Finger-like protrusions driven by actin polymerization.
- Hydrogel
-
A three-dimensional structure that 'behaves' like a solid owing to its crosslinked structure despite the fact that the bulkof its mass is comprised of water.
- Lamellipodia
-
Planar protrusions driven by actin polymerization.
- Linear and nonlinear elasticity
-
A mechanical property of compliant materials in which the elastic modulus is either independent of applied strain (linear elasticity) or increases dramatically as applied strain increases (nonlinear elasticity).
- Lobopodia
-
Blunt protrusions driven by contractility and intracellular pressure.
- Matrix metalloproteinase
-
(MMP). A major class of proteolytic enzymes that contain a metal ion, commonly Zn2+, within the catalytic site.
- Organotypic
-
A culture system that aims to recreate the organization of real tissue. For example, skin organotypic cultures include a lower collagen layer that mimics the dermis and an upper keratinocyte layer that is exposed to the air in a similar manner to skin. In some cases, these culture use matrices directly derived from animal or human tissue.
- Pseudopods
-
A broadly used term to describe protrusions that are formedby actin polymerization but lack the defined geometry of lamellipodia or filopodia.
- Second harmonic generation
-
(SHG). An imaging process that allows for the visualization of type I collagen fibrils. In this process two photons of incident light interact with the non-centrosymmetric structure of collagen to generate photons that are half the original wavelength.
- Stromal cell
-
Non-tumour cell that is found within tumours, such as leukocytes, fibroblasts and endothelial cells.
- Telopeptides
-
Non-helical portions of type I collagen fibrils that are located at both the amino- and carboxy-terminal ends of the fibril.Telopeptides support covalent crosslink formation.
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Friedl, P., Sahai, E., Weiss, S. et al. New dimensions in cell migration. Nat Rev Mol Cell Biol 13, 743–747 (2012). https://doi.org/10.1038/nrm3459
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DOI: https://doi.org/10.1038/nrm3459
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