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Bleb-based migration, a conserved cell motility mode, has a crucial role in both physiological and pathological processes. Unlike the well-elucidated mechanisms of lamellipodium-based mesenchymal migration, the dynamics of bleb-based migration remain less understood. In this review, we highlight in a systematic way the establishment of front-rear polarity, bleb formation and extension, and the distinct regimes of bleb dynamics. We emphasize new evidence proposing a regulatory role of plasma membrane-cortex interactions in blebbing behavior and discuss the generation of force and its transmission during migration. Our analysis aims to deepen the understanding of the physical and molecular mechanisms of bleb-based migration, shedding light on its implications and significance for health and disease.
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http://dx.doi.org/10.1016/j.tcb.2024.02.009 | DOI Listing |
bioRxiv
July 2025
Department of Regenerative and Cancer Cell Biology, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208.
Bleb-based migration enables cancer cells to navigate the heterogeneous tumor microenvironment. Here, we report a phenotypic screen identifying drugs that inhibit bleb formation, a driver of amoeboid migration. Statins, including Fluvastatin and Pitavastatin, suppress amoeboid migration of melanoma cells in confined environments by reducing intracellular cholesterol.
View Article and Find Full Text PDFNat Mater
September 2025
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Cell migration in mechanically confined environments is a crucial step of metastatic cancer progression. Nonetheless, the molecular components and processes mediating such behaviour are still not fully understood. Here we demonstrate that a pool of the scaffolding protein anillin and its cofactor Ect2, which are both predominantly nuclear proteins and critical mediators of cytokinesis, is present in the cytoplasm of multiple interphase cell types that promote confined cell migration.
View Article and Find Full Text PDFAdv Sci (Weinh)
June 2025
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Leukocytes forge paths through interstitial spaces by exerting forces to overcome confining mechanical pressures provided by surrounding cells. While such mechanical cues regulate leukocyte motility, engineering an in vitro system that models the deformable cellular environment encountered in vivo has been challenging. Here, microchannels are constructed with a liquid-liquid interface that exerts confining pressures similar to cells in tissues, and thus, is deformable by cell-generated forces.
View Article and Find Full Text PDFbioRxiv
January 2025
Cell and Developmental Biology Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, United States.
Cells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastatic melanoma cells migrating in non-adhesive confinement. Using high-resolution time-lapse imaging and specific molecular perturbations, we found that EGF signaling via PI3K stabilizes and maintains a polarized leader bleb.
View Article and Find Full Text PDFCurr Opin Cell Biol
October 2024
Regenerative and Cancer Cell Biology, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA. Electronic address:
Challenging mechanochemical environments (i.e., with varied mechanical and adhesive properties) are now known to induce a wide range of adaptive phenomena in motile cells.
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