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Analysis of barotactic and chemotactic guidance cues on directional decision-making of Dictyostelium discoideum cells in confined environments

Significance Cells confined in complex environments use a combination of chemical and mechanical cues for robust pathfinding and effective migration. Analysis of directional “decision-making” of Dictyostelium discoideum cells migrating within microchannels harboring asymmetric bifurcations shows that unlike neutrophils and immature dendritic cells Dictyostelium cells use chemical rather than barotactic guidance cues. Cells in steeper adenosine 3′,5′-cyclic monophosphate gradients migrating at higher speeds split their leading edges more readily when confronted with a bifurcation in the channel. The point at which one of the competing pseudopods starts to retract appears to be dependent on a relative force imbalance between two competing pseudopods, showing that cellular mechanics plays a major role in leading-edge dynamics, including front splitting, polarization, and retraction in D. discoideum. Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model organism Dictyostelium discoideum using a microfluidic chip design. This design allowed us to monitor the behavior of single cells via live imaging when confronted with bifurcating microchannels, presenting different combinations of hydraulic and chemical stimuli. Under the conditions employed we find no evidence in support of a barotactic response; the cells base their directional choices on the chemotactic cues. When the cells are confronted by a microchannel bifurcation, they often split their leading edge and start moving into both channels, before a decision is made to move into one and retract from the other channel. Analysis of this decision-making process has shown that cells in steeper nonhydrolyzable adenosine- 3', 5'- cyclic monophosphorothioate, Sp- isomer (cAMPS) gradients move faster and split more readily. Furthermore, there exists a highly significant strong correlation between the velocity of the pseudopod moving up the cAMPS gradient to the total velocity of the pseudopods moving up and down the gradient over a large range of velocities. This suggests a role for a critical cortical tension gradient in the directional decision-making process.