<p>Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal endocytic vesicle accumulation at cell front and filamentous actin assembly at cell rear in a polarized manner. These processes are interconnected and require Plexin-B2 signaling. We further show that Plexin-B2 governs membrane tension and other membrane features such as endocytosis, phospholipid composition, and inner leaflet surface charge, thus providing biophysical mechanisms by which Plexin-B2 promotes GBM invasion. Together, our studies unveil how GBM cells regulate membrane tension and mechano-electrical coupling to adapt to physical constraints and achieve polarized confined migration.</p>

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Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2

  • Chrystian Junqueira Alves,
  • Theodore Hannah,
  • Sita Sadia,
  • Christy Kolsteeg,
  • Angela Dixon,
  • Robert J. Wiener,
  • Ha Nguyen,
  • Murray J. Tipping,
  • Júlia Silva Ladeira,
  • Paula Fernandes da Costa Franklin,
  • Nathália de Paula Dutra de Nigro,
  • Rodrigo Alves Dias,
  • Priscila V. Zabala Capriles,
  • José P. Rodrigues Furtado de Mendonça,
  • Paul A. Slesinger,
  • Kevin D. Costa,
  • Hongyan Zou,
  • Roland H. Friedel

摘要

Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal endocytic vesicle accumulation at cell front and filamentous actin assembly at cell rear in a polarized manner. These processes are interconnected and require Plexin-B2 signaling. We further show that Plexin-B2 governs membrane tension and other membrane features such as endocytosis, phospholipid composition, and inner leaflet surface charge, thus providing biophysical mechanisms by which Plexin-B2 promotes GBM invasion. Together, our studies unveil how GBM cells regulate membrane tension and mechano-electrical coupling to adapt to physical constraints and achieve polarized confined migration.