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Related Experiment Video

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Cells use molecular working memory to navigate in changing chemoattractant fields.

Akhilesh Nandan1, Abhishek Das1, Robert Lott1

  • 1Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Elife
|June 6, 2022
PubMed
Summary

Cells use a molecular working memory to navigate complex chemical signals. This mechanism allows for persistent directional migration and adaptation to changing environments, revealing insights into cellular navigation.

Keywords:
EGF-induced migrationchanging environmentscriticalityhumanmolecular working memoryphysics of living systemsreal-time navigationsingle cell polarization

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Area of Science:

  • Cell Biology
  • Biophysics
  • Systems Biology

Background:

  • Cells migrate over long distances by sensing chemical gradients.
  • Existing mechanisms struggle to explain persistent migration amidst disrupted or changing signals.
  • Cellular adaptation to dynamic signaling environments remains poorly understood.

Purpose of the Study:

  • To elucidate the molecular mechanism enabling persistent directional cell migration in response to irregular and changing chemical cues.
  • To investigate how cells maintain directional persistence while adapting to dynamic signal localization.
  • To identify the computational principles underlying cellular navigation in complex chemoattractant fields.

Main Methods:

  • Theoretical derivation of receptor network dynamics.
  • Time-resolved live-cell imaging of Epidermal Growth Factor Receptor (EGFR) phosphorylation.
  • Analysis of signaling state metastability and remnant dynamics.

Main Results:

  • Cells employ a molecular working memory mechanism for directional migration.
  • A transiently polarized signaling state acts as a 'ghost' to guide migration.
  • This metastable state allows for adaptive responses to new signal encounters.
  • EGFR phosphorylation dynamics reveal memory-guided persistent migration.

Conclusions:

  • Cells utilize a novel working memory mechanism for navigation in dynamic chemoattractant fields.
  • The identified mechanism balances directional persistence with environmental adaptability.
  • This study reveals fundamental principles of real-time computation in cellular navigation.