Directional cell migration normally relies on a variety of external signals, such as chemical, mechanical, or electrical, which instruct cells in which direction to move. Many of the major molecular and physical effects derived from these cues are now understood, leading to questions about whether directional cell migration is alike or distinct under these different signals, and how cells might be directed by multiple simultaneous cues, which would be expected in complex in vivo environments. In this review, we compare how different stimuli are spatially distributed, often as gradients, to direct cell movement and the mechanisms by which they steer cells. A comparison of the downstream effectors of directional cues suggests that different external signals regulate a common set of components: small GTPases and the actin cytoskeleton, which implies that the mechanisms downstream of different signals are likely to be closely related and underlies the idea that cell migration operates by a common set of physical principles, irrespective of the input.
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