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Detecting long-range interactions between migrating cells.

C Metzner1, F Hörsch2, C Mark2

  • 1Biophysics, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. claus.metzner@gmail.com.

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This study introduces a new method to distinguish chemotaxis from random cell migration using p-values from cell trajectory analysis. The method revealed cooperative behavior in natural killer (NK) cells and differential interactions with tumor cells.

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Area of Science:

  • Cellular biology
  • Immunology
  • Computational biology

Background:

  • Chemotaxis is crucial for cells to navigate towards chemical signals, but distinguishing it from random movement is challenging.
  • Visual observation of cell-target encounters doesn't confirm chemotaxis, as random migration can lead to chance encounters.
  • Objective methods are needed to differentiate directed cell migration from random cell movement.

Purpose of the Study:

  • To develop and validate an objective method for distinguishing chemotactic cell migration from blind migration.
  • To analyze cell-cell interactions, specifically focusing on natural killer (NK) cells and K562 tumor cells.
  • To investigate cooperative and repulsive interactions in immune and tumor cell systems.

Main Methods:

  • Analysis of time-lapse recorded cell migration trajectories.
  • Computation of p-values for each movement step relative to a target's position, assessing likelihood under random migration.
  • Comparison of pooled p-value distributions against randomized target position reference distributions; validated with simulated data and applied to NK and K562 cells in 3D collagen gels.

Main Results:

  • The method reliably detected the presence or absence of remote cell-cell interactions in simulated data.
  • Attractive interactions were observed between natural killer (NK) cells from one donor, suggesting cooperative behavior.
  • Repulsive interactions were found between K562 tumor cells and NK cells from one donor, while IL-15 secreting K562 cells showed attraction to NK cells.

Conclusions:

  • The developed p-value method effectively differentiates chemotaxis from random migration, providing a tool for analyzing collective cell behavior.
  • NK cells exhibit donor-specific interactions, including cooperation and differential responses to tumor cells.
  • NK cells may find wild-type tumor cells by chance but are programmed to disengage, whereas they are attracted to IL-15 secreting tumor cells.