Figure 7: Summary of responses of LEGI-BEN to temporal and spatial stimuli.

(a) Modular view of the chemotaxis signalling pathway. The LEGI module senses chemoattractant stimuli and biases the activity of the STEN, which regulates the cytoskeleton. Polarity, which depends on the existence of an intact cytoskeleton, provides feedback by further biasing the STEN’s activity⁴⁸. The LEGI module (right) includes excitor (E) and inhibitor (I) elements that are regulated by receptor occupancy (S) and regulate the response regulator (RR) in complementary ways. (b) Response to multiple stimuli. Chemoattractants S1 and S2 activate different LEGI modules, which in turn regulate the same STEN that is coupled to the cytoskeletal network to mediate chemotaxis. (c) Summary of responses to temporal sequences and spatial gradients of chemoattractant. On the left, two stimuli separated by an interval trigger rapid changes in the excitor and slower changes in the inhibitor, which control the level of the response regulator. When the level of the response regulator crosses the threshold, it triggers the activation of STEN, which is all-or-none for each element on the membrane but may not be uniform across the whole cell (arrows)³¹. In a stable gradient, the excitor and inhibitor are generated by the local level of receptor occupancy, but as the inhibitor has a larger dispersion range (determined by its the diffusion rate and half-life⁶³) its steady-state distribution is shallower than that of the excitor. Consequently, the response regulator is higher than the threshold at the front and lower than the threshold at the back. This promotes persistent STEN activity at the front and when coupled to the cytoskeleton biases migration.