Cells use molecular working memory to navigate inchanging chemoattractant fields
Abstract
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.
Data availability
Source data is provided with the submission. The numerical data used to generate the corresponding figures can be obtained from the codes deposited in https://github.com/akhileshpnn/Cell-memory.
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Funding
Max Planck Society
- Aneta Koseska
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Nandan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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