Understanding the mechanisms used by glioblastoma multiforme (GBM) cells to navigate and invade the brain may be valuable for combating this lethal brain cancer. The tight interstitial space in the brain imposes several physical constraints on GBM cells, and the mechanisms by which these cells overcome them are not well understood. Recently, the Friedel lab identified a Plexin-B2-dependent mechanism in GBM cells that drives changes in membrane tension and actin-dependent mechano-electrical coupling during invasion. The group utilized a microchannel model to study confined migration of GBM cells. In combination with live cell imaging probes, they determined that GBM cells enhanced their velocity in response to constriction. Utilizing F-actin and membrane-labeling probes, the group identified robust accumulation of F-actin at the rear zone and MemGlow-labeled endocytic vesicles at the leading edge. Small-molecule inhibitor studies were used to establish a link between endocytic vesicle formation at the cell front and f-actin assembly at the cell rear. Plexin-2B KO cells had elongated F-actin cell processes, increased membrane ruffling, and compromised confined migration. Functionally, the loss of Plexin-B2 led to altered membrane phospholipid composition and disrupted inner membrane surface charge to couple changes in endocytosis and F-actin in response to physical constraints. Cytoskeleton Inc.’s live cell probes – SPY555-Actin (Cat. # CY-SC202), MemGlow 488 (Cat. # MG01), MemGlow NR12A (Cat. # MG07), and Flipper-TR (Cat. # CY-SC020) -- were critical probes for analyzing changes in membrane and F-actin in their confined migration studies. These studies identify critical players like Plexin-B2 in mediating the interplay between membrane mechanics and mechano-electrical coupling in GBM cell confined migration.
Link to Citation:
Product Used in Citation:
MemGlow™ 488: Fluorogenic Membrane Probe (a member of the MEMBRIGHT™ family) (Cat # MG01)
MemGlow™ NR12A Membrane Polarity Probe (Cat # MG07)
Flipper-TR Kit for fluorescence cell membrane microscopy (Cat # CY-SC020)
