title: Cellular memory in eukaryotic chemotaxis.
abstract: Natural chemical gradients to which cells respond chemotactically are often dynamic, with both spatial and temporal components. A primary example is the social amoeba Dictyostelium, which migrates to the source of traveling waves of chemoattractant as part of a self-organized aggregation process. Despite its physiological importance, little is known about how cells migrate directionally in response to traveling waves. The classic back-of-the-wave problem is how cells chemotax toward the wave source, even though the spatial gradient reverses direction in the back of the wave. Here, we address this problem by using microfluidics to expose cells to traveling waves of chemoattractant with varying periods. We find that cells exhibit memory and maintain directed motion toward the wave source in the back of the wave for the natural period of 6 min, but increasingly reverse direction for longer wave periods. Further insights into cellular memory are provided by experiments quantifying cell motion and localization of a directional-sensing marker after rapid gradient switches. The results can be explained by a model that couples adaptive directional sensing to bistable cellular memory. Our study shows how spatiotemporal cues can guide cell migration over large distances.
authors.affiliation: Departments of Biology and Physics, University of California, San Diego, La Jolla, CA 92093; and.
authors.forename: Monica
authors.initials: M
authors.lastname: Skoge
authors.affiliation: Physics, University of California, San Diego, La Jolla, CA 92093; and.
authors.forename: Haicen
authors.initials: H
authors.lastname: Yue
authors.affiliation: Physics, University of California, San Diego, La Jolla, CA 92093; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Erickstad
authors.affiliation: Departments of Biology and Physics, University of California, San Diego, La Jolla, CA 92093; and.
authors.forename: Albert
authors.initials: A
authors.lastname: Bae
authors.affiliation: Center for Theoretical Biological Physics and Department of Bioengineering, Rice University, Houston, TX 77251.
authors.forename: Herbert
authors.initials: H
authors.lastname: Levine
authors.affiliation: Physics, University of California, San Diego, La Jolla, CA 92093; and rappel@physics.ucsd.edu agroisman@ucsd.edu wloomis@ucsd.edu.
authors.forename: Alex
authors.initials: A
authors.lastname: Groisman
authors.affiliation: Departments of Biology and rappel@physics.ucsd.edu agroisman@ucsd.edu wloomis@ucsd.edu.
authors.forename: William F
authors.initials: WF
authors.lastname: Loomis
authors.affiliation: Physics, University of California, San Diego, La Jolla, CA 92093; and rappel@physics.ucsd.edu agroisman@ucsd.edu wloomis@ucsd.edu.
authors.forename: Wouter-Jan
authors.initials: WJ
authors.lastname: Rappel
mesh_terms: D000465:Algorithms; D002633:Chemotaxis / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D044085:Microfluidics / Q000379:methods; D008954:Models, Biological; D009068:Movement / Q000502:physiology; D013997:Time Factors; D018631:ras Proteins / Q000378:metabolism
chemical_list: C489016:ras protein, Dictyostelium; D000242:Cyclic AMP; D018631:ras Proteins
keywords: cell motility; cell signaling; directional sensing; polarity