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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 () and Roland H. Friedel ()
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Chrystian Junqueira Alves: Icahn School of Medicine at Mount Sinai
Theodore Hannah: Icahn School of Medicine at Mount Sinai
Sita Sadia: Icahn School of Medicine at Mount Sinai
Christy Kolsteeg: Icahn School of Medicine at Mount Sinai
Angela Dixon: Case Western Reserve University
Robert J. Wiener: Icahn School of Medicine at Mount Sinai
Ha Nguyen: Icahn School of Medicine at Mount Sinai
Murray J. Tipping: Memorial Sloan Kettering Cancer Center
Júlia Silva Ladeira: Federal University of Juiz de Fora
Paula Fernandes da Costa Franklin: Federal University of Juiz de Fora
Nathália de Paula Dutra de Nigro: Federal University of Juiz de Fora
Rodrigo Alves Dias: Federal University of Juiz de Fora
Priscila V. Zabala Capriles: Federal University of Juiz de Fora
José P. Rodrigues Furtado de Mendonça: Federal University of Juiz de Fora
Paul A. Slesinger: Icahn School of Medicine at Mount Sinai
Kevin D. Costa: Icahn School of Medicine at Mount Sinai
Hongyan Zou: Icahn School of Medicine at Mount Sinai
Roland H. Friedel: Icahn School of Medicine at Mount Sinai

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-024-55056-6

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