title: Self-Generated Chemoattractant Gradients: Attractant Depletion Extends the Range and Robustness of Chemotaxis.
abstract: Chemotaxis is fundamentally important, but the sources of gradients in vivo are rarely well understood. Here, we analyse self-generated chemotaxis, in which cells respond to gradients they have made themselves by breaking down globally available attractants, using both computational simulations and experiments. We show that chemoattractant degradation creates steep local gradients. This leads to surprising results, in particular the existence of a leading population of cells that moves highly directionally, while cells behind this group are undirected. This leading cell population is denser than those following, especially at high attractant concentrations. The local gradient moves with the leading cells as they interact with their surroundings, giving directed movement that is unusually robust and can operate over long distances. Even when gradients are applied from external sources, attractant breakdown greatly changes cells' responses and increases robustness. We also consider alternative mechanisms for directional decision-making and show that they do not predict the features of population migration we observe experimentally. Our findings provide useful diagnostics to allow identification of self-generated gradients and suggest that self-generated chemotaxis is unexpectedly universal in biology and medicine.
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Tweedy
authors.affiliation: Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Knecht
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Mackay
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Insall
mesh_terms: D002465:Cell Movement; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis; D004023:Dictyostelium
chemical_list: D002630:Chemotactic Factors