Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 5, Pages 1267-1272Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1513289113
Keywords
confined cell migration; moesin; microtubules; chemotaxis; cell polarization
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Funding
- BioMEMS Resource Center Grant [P41 EB002503]
- Biological and Biotechnological Sciences Research Council Grant [BB/F021402]
- Brigham and Women's Renal Division funds
- National Science Foundation [BMMB 15-36616]
- MacArthur Fellowship
- Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science
- Biotechnology and Biological Sciences Research Council [BB/F021402/1] Funding Source: researchfish
- BBSRC [BB/F021402/1] Funding Source: UKRI
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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.
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