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Autologous chemotaxis at high cell density.

Michael Vennettilli1,2, Louis González1, Nicholas Hilgert2

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Cellular sensing of fluid flow (autologous chemotaxis) fails at high densities due to signal interference. This study reveals the critical density for sensing failure and unexpected reversed cell motion in dense environments.

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Area of Science:

  • Cellular Biology
  • Biophysics
  • Mathematical Modeling

Background:

  • Autologous chemotaxis enables cells to sense fluid flow direction by detecting secreted molecules.
  • High cell densities disrupt this process as individual cell signals are overwhelmed by collective molecular interference.
  • This phenomenon is observed in metastatic cancer cells within dense tumor microenvironments.

Purpose of the Study:

  • To determine the critical cell density at which autologous chemotaxis sensing fails.
  • To derive a physical limit for autologous chemotaxis based on key parameters.
  • To investigate the implications of signaling molecule oversaturation on cell sensing and motion.

Main Methods:

  • Development and analysis of a minimal mathematical model for autologous chemotaxis.
  • Derivation of a physical limit for sensing based on cell density, Péclet number, and relevant lengthscales.
  • Comparison of model predictions with experimental observations of metastatic cancer cells.

Main Results:

  • The model accurately predicts the cell density at which autologous chemotaxis fails, aligning with experimental data.
  • A physical limit for autologous chemotaxis is established, quantifying the interplay of density and environmental factors.
  • In oversaturated environments, sensing failure can lead to reversed cell motion, indicating a breakdown of directional sensing.

Conclusions:

  • High cell density is a critical factor limiting the efficacy of autologous chemotaxis.
  • The derived physical limit provides a framework for understanding sensing failure in cellular collectives.
  • Reversed cell motion under oversaturation highlights complex mechanochemical sensing behaviors relevant to cancer cell invasion.