Proteolysis-free amoeboid migration of melanoma cells through crowded environments via bleb-driven worrying

Meghan K. Driscoll, Erik Welf, Andrew Weems, Etai Sapoznik, Felix Y Zhou, Vasanth S. Murali, Juan Manuel García-Arcos, Minna Roh-Johnson, Matthieu Piel, Kevin Dean, Reto P Fiolka, Gaudenz Danuser

Research output: Contribution to journalArticlepeer-review

Abstract

In crowded microenvironments, migrating cells must find or make a path. Amoeboid cells are thought to find a path by deforming their bodies to squeeze through tight spaces. Yet, some amoeboid cells seem to maintain a near-spherical morphology as they move. To examine how they do so, we visualized amoeboid human melanoma cells in dense environments and found that they carve tunnels via bleb-driven degradation of extracellular matrix components without the need for proteolytic degradation. Interactions between adhesions and collagen at the cell front induce a signaling cascade that promotes bleb enlargement via branched actin polymerization. Large blebs abrade collagen, creating feedback between extracellular matrix structure, cell morphology, and polarization that enables both path generation and persistent movement.

Original languageEnglish (US)
JournalDevelopmental cell
DOIs
StateAccepted/In press - 2024

Keywords

  • amoeboid
  • blebbing
  • cell migration
  • computer vision
  • extracellular matrix remodeling
  • fluorescence microscopy
  • light-sheet microscopy
  • macropinocytosis
  • melanoma

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • Developmental Biology
  • Cell Biology

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