Soft Matter Physics Meets Cell Biology: Transitions of Collective Cell Migration in 3D Environments

Plasticity of cell migration is a hallmark of cell movement during morphogenesis, tissue repair, and cancer metastasis. Interconversions of migration modes are tissue context-dependent and range from (1) collective migration of cohesive cells, migrating as epithelial sheets and strands; (2) multicellular networks of individualized cells moving while maintaining short-lived interactions; and (3) fully individualized cells moving by mesenchymal or amoeboid migration. Modes of cell migration, which are controlled by cell-cell adhesion, cell density, and active forces, can also be represented by physics-derived parameters, including temperature, applied stress, and volume fraction in classical passive jamming phase diagrams. Cell-packing density, cell-cell adhesion strength, and intrinsic migratory capacity have been defined as the key parameters driving jamming transitions in 2D sheet models, where extracellular matrix (ECM) is typically not considered. Here, we review how plasticity of cell migration programs intersects with jamming/unjamming principles and specifically focus on the impact of ECM architectures. In three-dimensional (3D) tissues, additional spatial parameters determine cell density and cell-cell interactions, including the degree of confinement forcing cells together versus the availability of free space. Integrating mechanisms of jamming/unjamming with actin-based active movement of cells in a 3D environment, similar to the motion of active nematic droplets in a passive nematic matrix, will enable building realistic models to predict cell behaviors in physiological and pathological contexts, including cancer metastasis.