Orientation of chemotactic cells and growth cones: models and mechanisms.

A model is proposed for an amplification step in chemotactically sensitive cells or growth cones that accounts for their extraordinary directional sensitivity. It is assumed that cells have an intrinsic pattern forming system that generates the signals for extension of filopods and lamellipods. An external signal such as a graded cue is assumed to impose some directional preference onto the pattern formed. According to the model, a saturating, self-enhancing reaction is coupled with two antagonistic reactions. One antagonist equilibrates rapidly over the whole cell, causing competition between different surface elements of the cell cortex for activation. It will be won by those cortical regions of the cell that are exposed to the highest concentrations of the external graded cues. The second antagonistic reaction is assumed to act more locally and has a longer time constant. It causes a destabilization of peaks after they have formed. While the total activated area on the cell surface is maintained, the disappearance of some hot spots allows the formation of new ones, preferentially at positions specified by the actual external guiding signal. Computer simulations show that the model accounts for the highly dynamic behaviour of chemotactic cells and growth cones. In the absence of external signals, maxima of the internal signals emerge at random positions and disappear after some time. Travelling waves or oscillations in counter phase can emerge on the cell cortex, in agreement with observations reported in the literature. In other ranges of parameters, the model accounts for the generation of a stable cell polarity.