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Contact inhibition of locomotion is a contact-triggered change of protrusions and movement direction. It is distinct from contact inhibition of proliferation. In neural crest experiments, cell collisions caused protrusion collapse and repolarization; blocking noncanonical Wnt signalling disrupted the response.^[ref]

External chemical signals can guide cell migration, but the statement is too strong if “determined” means that they uniquely specify whether, how fast and in which direction a cell moves. A chemoattractant gradient biases a cell's internal polarity machinery; it does not directly supply the mechanical work of locomotion. Chemotaxis is directional bias, whereas a change in speed or persistence without directional preference is chemokinesis.

A chemical response depends on receptor abundance, signalling adaptation and the cell's existing cell polarity. The same external field can therefore yield different trajectories in different cell states. Uniform stimulation can increase motility without providing a direction, and spontaneous fluctuations of the actin system can initiate movement without a spatial chemical instruction. Persistent migration combines feedback within the cell with a cue that biases that feedback.

Mechanical and geometrical inputs also matter. Durotaxis describes a bias associated with substrate stiffness, while haptotaxis follows spatial variation in adhesive ligands. Contact guidance by fibre alignment can channel motion even when soluble signals are uniform. Narrow spaces constrain the available paths and can force a switch of protrusive mechanism. These effects are not wholly separate from chemistry: cells sense mechanical forces through molecular interactions. Nevertheless, their directional information resides in mechanics or geometry, not necessarily in an imposed soluble concentration gradient.

Contacts between cells supply another source of organization. Experiments on neural crest cells showed that collisions can cause protrusion collapse and repolarization, and that perturbing noncanonical Wnt signalling disrupts this behaviour and group directionality.^[ref] Contact inhibition of locomotion therefore helps generate collective trajectories through local interactions, rather than each cell independently reading a complete external chemical map. Cohesion and other attractive interactions can prevent such repulsion from simply dispersing the group.

A discriminating experiment independently varies soluble gradient, adhesive pattern and mechanical confinement. Measure direction, speed and persistence separately; reverse the gradient, remove it, and then block the relevant receptor while checking viability and the ability to move. If a directional bias follows the reversed chemical field, that supports chemical guidance. If speed rises under uniform stimulation, that supports chemokinesis. If trajectories remain aligned with fibres after chemical reversal, physical guidance is influential. Manipulating intracellular polarity can test whether a cue is instructive or merely permissive.

The useful conclusion is that motion emerges from an internally powered, state-dependent cell interacting with chemical, mechanical and cellular surroundings. External chemical signals are often decisive inputs, but the trajectory is a property of the coupled system.