title: Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells.
abstract: Chemotaxis, the directional migration of cells in a chemical gradient, is robust to fluctuations associated with low chemical concentrations and dynamically changing gradients as well as high saturating chemical concentrations. Although a number of reports have identified cellular behavior consistent with a directional memory that could account for behavior in these complex environments, the quantitative and molecular details of such a memory process remain unknown. Using microfluidics to confine cellular motion to a 1D channel and control chemoattractant exposure, we observed directional memory in chemotactic neutrophil-like cells. We modeled this directional memory as a long-lived intracellular asymmetry that decays slower than observed membrane phospholipid signaling. Measurements of intracellular dynamics revealed that moesin at the cell rear is a long-lived element that when inhibited, results in a reduction of memory. Inhibition of ROCK (Rho-associated protein kinase), downstream of RhoA (Ras homolog gene family, member A), stabilized moesin and directional memory while depolymerization of microtubules (MTs) disoriented moesin deposition and also reduced directional memory. Our study reveals that long-lived polarized cytoskeletal structures, specifically moesin, actomyosin, and MTs, provide a directional memory in neutrophil-like cells even as they respond on short time scales to external chemical cues.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115; Renal Division, Brigham and Women's Hospital, Boston, MA 02115; Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
authors.forename: Harrison V
authors.initials: HV
authors.lastname: Prentice-Mott
authors.affiliation: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Meroz
authors.affiliation: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
authors.forename: Andreas
authors.initials: A
authors.lastname: Carlson
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115; Renal Division, Brigham and Women's Hospital, Boston, MA 02115;
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
authors.affiliation: National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310;
authors.forename: Michael W
authors.initials: MW
authors.lastname: Davidson
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Boston, MA 02129;
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
authors.affiliation: London Centre for Nanotechnology, University College London, London WC1H 0AH, United Kingdom; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom;
authors.forename: Guillaume T
authors.initials: GT
authors.lastname: Charras
authors.affiliation: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Department of Physics, Harvard University, Cambridge, MA 02138; Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138; Kavli Institute for Nanobio Science and Technology, Harvard University, Cambridge, MA 02138 lm@seas.harvard.edu jagesh_shah@hms.harvard.edu.
authors.forename: L
authors.initials: L
authors.lastname: Mahadevan
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115; Renal Division, Brigham and Women's Hospital, Boston, MA 02115; lm@seas.harvard.edu jagesh_shah@hms.harvard.edu.
authors.forename: Jagesh V
authors.initials: JV
authors.lastname: Shah
mesh_terms: D016764:Cell Polarity; D002633:Chemotaxis; D003599:Cytoskeleton / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007156:Immunologic Memory
keywords: cell polarization; chemotaxis; confined cell migration; microtubules; moesin