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Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy
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Cell protrusion and retraction driven by fluctuations in actin polymerization: A two-dimensional model.

Gillian L Ryan1,2, Danielle Holz2, Sawako Yamashiro3

  • 1Department of Physics, Kettering University, 1700 University Avenue, Flint, Michigan, 48504.

Cytoskeleton (Hoboken, N.J.)
|July 29, 2017
PubMed
Summary

This study models cell protrusion dynamics using a 2D actin network model. It reveals how actin polymerization, influenced by concentration and membrane forces, drives cell lamellipodia movement and retraction.

Keywords:
actin polymerizationcell motilityexcitable dynamicslamellipodiummathematical modeling

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Area of Science:

  • Cell Biology
  • Biophysics
  • Computational Biology

Background:

  • Animal cells use actin-rich lamellipodia for surface spreading and protrusion.
  • Cells exhibit lamellipodial protrusion and retraction patterns, even when stationary.
  • Previous models linked XTC cell protrusion fluctuations to 1D actin dynamics.

Purpose of the Study:

  • Extend a 1D actin dynamics model to 2D to simulate cell lamellipodia protrusion and retraction.
  • Investigate the role of actin polymerization rate changes in response to local concentration and membrane forces.
  • Reproduce experimentally observed patterns of membrane dynamics and F-actin fluctuations.

Main Methods:

  • Developed a 2D model of actin dynamics incorporating arc-length and radial directions.
  • Included a model cell membrane that responds to changes in actin filament barbed ends.
  • Simulated Brownian ratchet and switch-like force-velocity relationships for actin polymerization.

Main Results:

  • The 2D model successfully reproduces experimental patterns of membrane protrusion and retraction.
  • Actin polymerization rate modulation by local concentration and membrane force is key to observed dynamics.
  • Switch-like polymerization dynamics accurately predict F-actin concentration fluctuations.

Conclusions:

  • The 2D model provides a mechanistic explanation for cell lamellipodia protrusion and retraction patterns.
  • Actin dynamics are sensitive to local feedback mechanisms involving filament concentration and membrane tension.
  • The model offers testable predictions for cell behavior under membrane tension perturbations.