A two-step search and run response to gradients shapes leukocyte navigation in vivo.


Type
Article
Change log
Abstract

Migrating cells must interpret chemical gradients to guide themselves within tissues. A long-held principle is that gradients guide cells via reorientation of leading-edge protrusions. However, recent evidence indicates that protrusions can be dispensable for locomotion in some contexts, raising questions about how cells interpret endogenous gradients in vivo and whether other mechanisms are involved. Using laser wound assays in zebrafish to elicit acute endogenous gradients and quantitative analyses, we demonstrate a two-stage process for leukocyte chemotaxis in vivo: first a "search" phase, with stimulation of actin networks at the leading edge, cell deceleration, and turning. This is followed by a "run" phase, with fast actin flows, cell acceleration, and persistence. When actin dynamics are perturbed, cells fail to resolve the gradient, suggesting that pure spatial sensing of the gradient is insufficient for navigation. Our data suggest that cell contractility and actin flows provide memory for temporal sensing, while expansion of the leading edge serves to enhance gradient sampling.

Description
Keywords
Actins, Animals, Chemotaxis, Leukocyte, Leukocytes, Zebrafish
Journal Title
J Cell Biol
Conference Name
Journal ISSN
0021-9525
1540-8140
Volume Title
Publisher
Rockefeller University Press
Sponsorship
Medical Research Council (MR/L019523/1)
Physiological Society (Unknown)
Isaac Newton Trust (Minute 19.23(n))
Leverhulme Trust (RPG-2021-226)
Wellcome Trust (105391/Z/14/Z)
Wellcome Trust (204845/Z/16/Z)