The Interplay between Cell Motility and Proteolysis in the Establishment of Brain Metastasis

We successfully engineered the CDM network labeled with fluorescent markers highlighting fibronectin a protein of the extracellular matrix, and we also observed the dynamics of key components driving cell migration, such as the actin cytoskeleton and focal contacts. Our results reveal key differences between 2D and 3D cell migration. (i) We report new types of protrusions distinct from filopodia/lamellipodia reported on planar surfaces, which are driven by pressure. (ii) Our 3D network is deformed reversibly during migration and this allows the extraction of forces locally applied by cells. We correlate these local forces to the focal contacts dynamics, and our measures indicate a local pulling mechanism for forward cell motion and nucleus translocation. (iii) During migration, the nucleus local deformation by the cytoskeleton is needed to facilitate motion. These three phenomena pressure-driven protrusions, local forces correlated to local focal contacts, and nucleus deformation driven by the cytoskeleton are reproduced in microchannels matching cell dimensions. Altogether, our results show that mechanical confinement of cell and nucleus is the main cause for differences between 3D and 2D motions.