Cooperation, competition, and conviction in decision-making for motile cells

Efficient chemotaxis requires close coordination between the front and the rear of a migrating cell. For rapidly migrating neutrophils, persistent polarization is maintained by mutual antagonism between signaling networks active at the front versus those active at the rear. In addition, the structural organization of the actin cytoskeleton at the protruding front, dominated by a dendritically branched growing filament network, is dramatically different from the organization at the rear, dominated by myosin II contractility. Coordination between the front and the rear is mediated by mechanical feedback mechanisms, including cell-scale retrograde actin network flow, membrane tension, and dynamic myosin relocalization, that are optimized to balance migration persistence with turning efficiency. The generally stable state where individual migrating neutrophils maintain one front and one rear over many minutes can be disrupted when cells encounter obstacles that split the leading edge, causing the formation of multiple fronts. We have used microfluidic channels to establish a reproducible geometry for forcing cells to make a decision to convert one of two equally sized competing fronts into a retracting rear. The decision can be biased by optogenetic stimulation of the chemoattractant signaling pathway on one of the two competing fronts, but only during the latest stages of decision-making, indicating that both protruding fronts and retracting rears are generally unresponsive to changing stimuli unless mechanical competition has begun to “raise doubt”, rendering them amenable to reprogramming.