Comparison of cell migration mechanical strategies in three-dimensional matrices: A computational study

Cell migration on a two-dimensional flat surface has been extensively studied and is generally characterized by a front-protrusion–rearcontraction process. In a three-dimensional (3D) environment, on the other hand, cells adopt multiple migration strategies depending on the cell type and the properties of the extracellular matrix (ECM). By using computer simulations, we find that these migration strategies can be classified by various spatial–temporal dynamics of actin protrusion, actin–myosin contraction and actin–ECM adhesion. We demonstrate that if we include or exclude proteolysis of ECM, and vary adhesion dynamics and spatial distributions of protrusion, contraction and adhesion, our model can reproduce six experimentally observed motility modes: mesenchymal, chimneying, amoeboid, blebbing, finger-like protrusion and rear-squeezing cell locomotory behaviours. We further find that the mode of the cell motility evolves in response to the ECM density and adhesion detachment rate. The model makes non-trivial predictions about cell speed as a function of the adhesion strength, and ECM elasticity and mesh size.