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Adhesion-Dependent Wave Generation in Crawling Cells.

Erin L Barnhart1, Jun Allard2, Sunny S Lou3

  • 1Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Summary
This summary is machine-generated.

Cellular actin networks exhibit excitability, generating protrusion waves. Increased cell adhesion strengthens interactions, leading to VASP depletion and wave formation, a process modeled mathematically.

Keywords:
VASPactin dynamicsactin wavesadhesion dynamicscell motilityexcitable systemkeratocyteleading edge

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Area of Science:

  • Cell Biology
  • Biophysics
  • Cytoskeleton Dynamics

Background:

  • Dynamic actin networks in migrating cells exhibit excitability, leading to traveling waves of protrusion.
  • Disentangling molecular and mechanical factors in wave generation is challenging due to complex cell morphodynamics.

Purpose of the Study:

  • Define mechanochemical feedback loops underlying actin network excitability and wave generation.
  • Investigate the role of VASP (vasodilator-stimulated phosphoprotein) in protrusion wave dynamics.

Main Methods:

  • Utilized fish epithelial keratocytes, a simple cell model.
  • Manipulated cell-substrate adhesion strength.
  • Overexpressed VASP.
  • Developed and simulated a mathematical model of protrusion waves.

Main Results:

  • Increased cell-substrate adhesion induced waving protrusion in keratocytes.
  • Protrusion waves result from fluctuations in actin polymerization rates.
  • VASP overexpression switched highly adherent keratocytes from waving to persistent protrusion.
  • VASP depletion by adhesions, actin network architecture, and membrane mechanics drive wave formation.
  • VASP localization at the leading edge oscillates, peaking before protrusion initiation.

Conclusions:

  • Mechanochemical feedback loops involving VASP, adhesions, and actin dynamics generate protrusion waves in keratocytes.
  • These feedback mechanisms may represent a general module for excitable actin dynamics in various cell types.