Ankita Jha «Blebology- Blebs in cell migration and cancer disease progression»

Blebs are dynamic membrane protrusions increasingly recognized as active regulators of signaling and cell behavior. In this talk, I will present how bleb morphology organizes intracellular signaling to drive migration in metastatic melanoma, particularly under confined, low-adhesion environments. Unlike mesenchymal migration, bleb-based motility relies on large, pressure-driven leader blebs that define cell polarity. Using high-resolution live imaging, molecular perturbations, and optogenetics, we show that growth factor receptor-PI3K signaling is essential for maintaining a stable, polarized bleb. We further identify that transmembrane picket protein CD44 and membrane-cortex linkers restrict receptor mobility on the plasma membrane at the bleb rear, supporting a spatial signaling gradient crucial for persistent migration. Our combined experimental and modeling approaches reveal a feedback loop between cortical architecture and signaling, establishing a novel polarity axis. These findings highlight how membrane organization enables migratory plasticity, allowing tumor cells to adapt to physical constraints during metastasis. This work also underscores how distinct spatial arrangements of conserved signaling modules on the membrane enable plasticity in migration strategies, allowing metastatic cells to adapt to biophysical constraints of the tumor microenvironment