As individual cells or groups of cells move through the complex environment of the body, their migration is affected by multiple external cues. Some cues are diffusible signaling molecules, and some are solid biophysical features. How do cells respond appropriately? This perspective discusses the relationship between guidance input and the cellular output, considering effects from classical chemotaxis to contact-dependent guidance. The influences of membrane trafficking and of imposed constraints on directional movement are also considered. New insights regarding guidance and dynamic cell polarity have emerged from examining new cell migration models and from re-examining well known ones with new approaches and new tools.
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