Protrusive waves guide 3D cell migration along nanofibers

In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell mi...

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Bibliographic Details
Published in:The Journal of cell biology 2015-11, Vol.211 (3), p.683-701
Main Authors: Guetta-Terrier, Charlotte, Monzo, Pascale, Zhu, Jie, Long, Hongyan, Venkatraman, Lakshmi, Zhou, Yue, Wang, PeiPei, Chew, Sing Yian, Mogilner, Alexander, Ladoux, Benoit, Gauthier, Nils C
Format: Article
Language:English
Subjects:
3-D technology
3T3 Cells
Actins - metabolism
Actomyosin - metabolism
Animals
Cell adhesion & migration
Cell Adhesion - physiology
Cell Line
Cell Line, Tumor
Cell Movement - physiology
Cellular Biology
Dogs
Extracellular Matrix - metabolism
Extracellular Matrix - physiology
Fibronectins - metabolism
HEK293 Cells
HeLa Cells
Human Umbilical Vein Endothelial Cells
Humans
Life Sciences
Madin Darby Canine Kidney Cells
Mice
NIH 3T3 Cells
PC12 Cells
Rats
Signal Transduction - physiology
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Summary:In vivo, cells migrate on complex three-dimensional (3D) fibrous matrices, which has made investigation of the key molecular and physical mechanisms that drive cell migration difficult. Using reductionist approaches based on 3D electrospun fibers, we report for various cell types that single-cell migration along fibronectin-coated nanofibers is associated with lateral actin-based waves. These cyclical waves have a fin-like shape and propagate up to several hundred micrometers from the cell body, extending the leading edge and promoting highly persistent directional movement. Cells generate these waves through balanced activation of the Rac1/N-WASP/Arp2/3 and Rho/formins pathways. The waves originate from one major adhesion site at leading end of the cell body, which is linked through actomyosin contractility to another site at the back of the cell, allowing force generation, matrix deformation and cell translocation. By combining experimental and modeling data, we demonstrate that cell migration in a fibrous environment requires the formation and propagation of dynamic, actin based fin-like protrusions.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201501106