TY - JOUR TI - Cells use molecular working memory to navigate in changing chemoattractant fields AU - Nandan, Akhilesh AU - Das, Abhishek AU - Lott, Robert AU - Koseska, Aneta A2 - Murugan, Arvind A2 - Barkai, Naama A2 - Jerison, Elizabeth R VL - 11 PY - 2022 DA - 2022/06/06 SP - e76825 C1 - eLife 2022;11:e76825 DO - 10.7554/eLife.76825 UR - https://doi.org/10.7554/eLife.76825 AB - 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. KW - real-time navigation KW - changing environments KW - molecular working memory KW - EGF-induced migration KW - criticality KW - single cell polarization JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -