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

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.

Biased migration of confined neutrophil-like cells in asymmetric hydraulic environments.

Cells integrate multiple measurement modalities to navigate their environment. Soluble and substrate-bound chemical gradients and physical cues have all been shown to influence cell orientation and migration. Here we investigate the role of asymmetric hydraulic pressure in directional sensing. Cells confined in microchannels identified and chose a path of lower hydraulic resistance in the absence of chemical cues. In a bifurcating channel with asymmetric hydraulic resistances, this choice was preceded by the elaboration of two leading edges with a faster extension rate along the lower resistance channel. Retraction of the "losing" edge appeared to precipitate a final choice of direction. The pressure differences altering leading edge protrusion rates were small, suggesting weak force generation by leading edges. The response to the physical asymmetry was able to override a dynamically generated chemical cue. Motile cells may use this bias as a result of hydraulic resistance, or "barotaxis," in concert with chemotaxis to navigate complex environments.