Ratchetaxis: Long-Range Directed Cell Migration by Local Cues

Directed cell migration is usually thought to depend on the presence of long-range gradients of either chemoattractants or physical properties such as stiffness or adhesion. However, in vivo, chemical or mechanical gradients have not systematically been observed. Here we review recent in vitro experiments, which show that other types of spatial guidance cues can bias cell motility. Introducing local geometrical or mechanical anisotropy in the cell environment, such as adhesive/topographical microratchets or tilted micropillars, show that local and periodic external cues can direct cell motion. Together with modeling, these experiments suggest that cell motility can be viewed as a stochastic phenomenon, which can be biased by various types of local cues, leading to directional migration. Ratchetaxis is defined by the guiding effect of local and repeated anisotropic features in the cell environment. The features can be of physical or chemical nature.Ratchetaxis was experimentally proven in vitro and might also affect migration of cells through complex environments in vivo, with potential relevance for development and cancer.Potential players for the sensing of local anisotropic cues leading to ratchetaxis include cell protrusions as well as the cell nucleus/body.