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Related Experiment Video

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Creating Adhesive and Soluble Gradients for Imaging Cell Migration with Fluorescence Microscopy
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Cell Migration Driven by Self-Generated Integrin Ligand Gradient on Ligand-Labile Surfaces.

Anwesha Sarkar1, Dana N LeVine2, Natalia Kuzmina3

  • 1Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.

Current Biology : CB
|September 11, 2020
PubMed
Summary

Stationary cells become migratory by rupturing integrin ligands, creating a surface density gradient that drives movement. This novel ligand-depleting (LD) migration mechanism allows cells to move on dynamic substrates.

Keywords:
cell motilitydirectional cell migrationhaptotaxismatrix remodelingself-generated gradientsurface ligand gradienttension gauge tethertension sensor

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Area of Science:

  • Cell Biology
  • Biophysics
  • Biochemistry

Background:

  • Integrin-ligand interactions are crucial for cell adhesion and migration in multicellular organisms.
  • Cellular force can influence the stability and availability of integrin ligands on surfaces.

Purpose of the Study:

  • To identify and characterize a novel mode of cell migration driven by ligand lability.
  • To elucidate the biophysical mechanism underlying this new migration phenomenon.
  • To explore the potential biological significance of this migration mode.

Main Methods:

  • Utilized TGT (a rupturable molecular linker) to quantitatively control ligand rupture rates by cellular force.
  • Tested various cell types, including platelets and CHO-K1 cells, on TGT-functionalized surfaces.
  • Employed a combination of experimental assays and computational simulations to analyze cell migration and ligand dynamics.

Main Results:

  • Discovered that stationary cells spontaneously become motile on surfaces with labile integrin ligands.
  • Demonstrated that cell motility correlates with the rate of ligand depletion induced by cellular force.
  • Revealed that cells establish and maintain a ligand surface density gradient that drives directed migration, termed ligand-depleting (LD) migration.
  • Showcased that LD migration is analogous to self-propulsion mechanisms observed in non-living systems.

Conclusions:

  • Introduced ligand-depleting (LD) migration as a new mode of cell motility driven by the dynamic rupture of integrin ligands.
  • Established the biophysical basis of LD migration, involving the creation of a ligand density gradient that propels cell movement.
  • Highlighted the potential roles of LD migration in physiological processes, including immune cell function, platelet aggregation, and cancer cell metastasis, particularly on dynamic extracellular matrix environments.