Jamming Transitions in Astrocytes and Glioblastoma Are Induced by Cell Density and Tension

Collective behavior of cells emerges from coordination of cell-cell-interactions and is important to wound healing, embryonic and tumor development. Depending on cell density and cell-cell interactions, a transition from a migratory, fluid-like unjammed state to a more static and solid-like jammed state or vice versa can occur. Here, we analyze collective migration dynamics of astrocytes and glioblastoma cells using live cell imaging. Furthermore, atomic force microscopy, traction force microscopy and spheroid generation assays were used to study cell adhesion, traction and mechanics. Perturbations of traction and adhesion were induced via ROCK or myosin II inhibition. Whereas astrocytes resided within a non-migratory, jammed state, glioblastoma were migratory and unjammed. Furthermore, we demonstrated that a switch from an unjammed to a jammed state was induced upon alteration of the equilibrium between cell-cell-adhesion and tension from adhesion to tension dominated, via inhibition of ROCK or myosin II. Such behavior has implications for understanding the infiltration of the brain by glioblastoma cells and may help to identify new strategies to develop anti-migratory drugs and strategies for glioblastoma-treatment.

Automated summary

Collective behavior of cells is crucial for wound healing, embryonic and tumor development, and can undergo a transition from a migratory unjammed state to a static jammed state depending on cell density and interactions. This study investigated the collective migration dynamics of astrocytes and glioblastoma cells and explored cell adhesion, traction, and mechanics using various techniques. Results showed that astrocytes remained in a non-migratory jammed state, while glioblastoma cells exhibited migratory unjammed behavior. Switching between jammed and unjammed states could be induced by altering the balance between cell-cell adhesion and tension via inhibition of ROCK or myosin II. These findings are important for understanding glioblastoma cell infiltration and developing novel anti-migratory drugs and treatment strategies.