Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells

Harrison V. Prentice-Mott, Yasmine Meroz, Andreas Carlson, Michael A. Levine, Michael W. Davidson, Daniel Irimia, Guillaume T. Charras, L. Mahadevan, Jagesh V. Shah

Research output: Contribution to journalArticlepeer-review

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 longlived 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.

Original languageEnglish
Pages (from-to)1267-1272
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number5
DOIs
StatePublished - 2 Feb 2016
Externally publishedYes

Keywords

  • Cell polarization
  • Chemotaxis
  • Confined cell migration
  • Microtubules
  • Moesin

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