Three-dimensional cell migration does not follow a random walk

Significance The motility of cells in the absence of gradients has long been described in terms of random walks. Most of what we know about eukaryotic cell migration has stemmed from well-controlled studies of cell migration on flat dishes. However, cells in vivo often move through 3D environments. Despite this difference, cell speed and persistence are typically extracted from fits using the same persistence random walk (PRW) model. This paper shows that the assumptions of the PRW model are erroneous for 3D cell migration. We introduce and validate a new model of 3D cell migration that takes into account cell heterogeneity and the anisotropic movements induced by local remodeling of the 3D matrix.