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