In order to migrate over large distances, cells within tissues and organisms rely on sensing local gradient cues which are irregular, conflicting, and changing over time and space. The mechanism how they generate persistent directional migration when signals are disrupted, while still remaining adaptive to signal's localization changes remain unknown. Here we find that single cells utilize a molecular mechanism akin to a working memory to satisfy these two opposing demands. We derive theoretically that this is characteristic for receptor networks maintained away from steady states. Time-resolved live-cell imaging of Epidermal growth factor receptor (EGFR) phosphorylation dynamics shows that cells transiently memorize position of encountered signals via slow-escaping remnant of the polarized signaling state, a dynamical 'ghost', driving memory-guided persistent directional migration. The metastability of this state further enables migrational adaptation when encountering new signals. We thus identify basic mechanism of real-time computations underlying cellular navigation in changing chemoattractant fields.

In order to migrate over large distances, cells within tissues and organisms rely on sensing local gradient cues. These cues however are multifarious, irregular or conflicting, changing both in time and space. Here we find that single cells utilize a molecular mechanism akin to a working memory, to generate persistent directional migration when signals are disrupted by temporally memorizing their position, while still remaining adaptive to spatial and temporal changes of the signal source. Using dynamical systems theory, we derive that these information processing capabilities are inherent for protein networks whose dynamics is maintained away from steady state through organization at criticality. We demonstrate experimentally using the Epidermal growth factor receptor (EGFR) signaling network, that the memory is maintained in the prolonged receptor’s activity via a slow-escaping remnant, a dynamical ”ghost” of the attractor of the polarized signaling state, that further results in memory in migration. As this state is metastable, it also enables continuous adaptation of the migration direction when the signals vary in space and time. We therefore show that cells implement real-time computations without stable-states to navigate in changing chemoattractant fields by memorizing position of disrupted signals while maintaining sensitivity to novel chemical cues.