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.
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http://dx.doi.org/10.1038/s41467-024-55056-6 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697315 | PMC |
Biophys J
January 2025
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Center for Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv, Israel. Electronic address:
Migrasomes, the vesicle-like membrane micro-structures, arise on the retraction fibers (RFs), the branched nano-tubules pulled out of cell plasma membranes during cell migration and shaped by membrane tension. Migrasomes form in two steps: a local RF bulging is followed by a protein-dependent stabilization of the emerging spherical bulge. Here we addressed theoretically and experimentally the previously unexplored mechanism of bulging of membrane tubular systems.
View Article and Find Full Text PDFNat Commun
January 2025
Center for Physics and Chemistry of Living Systems, Tel Aviv University, Tel Aviv, Israel.
Propagation of membrane tension mediates mechanical signal transduction along surfaces of live cells and sets the time scale of mechanical equilibration of cell membranes. Recent studies in several cell types and under different conditions revealed a strikingly wide variation range of the tension propagation speeds including extremely low ones. The latter suggests a possibility of long-living inhomogeneities of membrane tension crucially affecting mechano-sensitive membrane processes.
View Article and Find Full Text PDFNat Commun
January 2025
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
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.
View Article and Find Full Text PDFZhonghua Kou Qiang Yi Xue Za Zhi
January 2025
Department of Orthodontic Dentistry, School of Stomatology, The Fourth Military Medical University, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Xi'an710032, China.
To explore the distribution characteristics of glioma-associated oncogene homolog 1 (Gli1) positive cells during orthodontic tooth movement process and conduct a proteomic analysis of these cells. Forty Gli1-LacZ transgenic mice were used to establish an in orthodontic tooth movement (OTM) model for labeling Gli1 positive cells in Gli1-LacZ transgenic mice (OTM group) and an unforced control group, with tooth movement distance measured using micro-CT. The spatial relationship and distribution characteristics of Gli1 positive cells and H-type vessels of CD31 and endomucin (EMCN) in periodontal tissues were detected by immunofluorescence staining.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
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