Abstract
Biopolymer networks such as collagen or fibrin gels are frequently used to study tumour cell migration in a three-dimensional (3-D) environment. The mechanical properties of such networks are generally characterized by strain stiffening under shear and strong lateral contraction under stretch. Unlike on planar substrates where cell traction forces increase with matrix stiffness, traction forces in 3-D are independent of matrix stiffness. Time-lapse force microscopy reveals that cells migrate through a 3-D biopolymer network in a gliding motion with alternating phases of simultaneously high or low contractility, elongation, migratory speed, and persistence. Furthermore, 3-D cell migration is enhanced by a higher network stiffness, opposite to cell behaviour in 2-D, as long as the pore size does not fall below a critical value where it causes excessive steric hindrance. To quantify the effect of steric hindrance on cell migration, we use linear arrays of sequentially narrowing 3-D microconstrictions with diameters from 12 µm down to 1.5 µm. Steric hindrance as measured by the stalling of the cells’ nuclei at the entrance of small microconstrictions becomes more prominent in poorly adhesive cells. By contrast, steric hindrance is only weakly correlated with high cell stiffness and low contractility. Taken together, these findings reveal fundamental differences in the migration behaviour of cells in a 2-D versus a 3-D environment, as well as large differences in the migration strategies between common tumour cell types.