Fig. 9. Possible mechanisms of SFICM. (A) Shear stress at the cell-substrate contact area facing the flow triggers two signaling pathways. One stimulates pseudopodium emission in every direction (+), whereas the other locally inhibits pseudopodium emission near the stressed zone. This latter local signal is related to PI3K activity, because its inhibition allows pseudopodium emission against the flow. (B) Cell detachment results from the competition between SFICM and passive membrane peeling. The solid and dotted lines depict the average front and rear edge speed as a function of applied shear flow, respectively, based on the values determined in Figs 3, 5. Closed squares: cell instant speed (Fig. 3). Open squares: peeling velocity (Fig. 5). For =6.2 Pa, the peeling velocity is approximated by the translational velocity of rapidly detaching cells and the front velocity by the instant speed of slowly detaching cells. The threshold stress for cell detachment _1/2 corresponds to the speed at which the average front edge velocity v_f cannot adapt to the average rear edge velocity v_r; v_p designates the burst growth rate and v_l the limit in front edge velocity leading to the detachment of 50% of the cells. The dotted line corresponds to the following equation: , with v₀ =(1.1±0.1)x10^–2µm second^–1 and ₀ =(8±0.5)x10^–2 Pa. The rationale for using this relation to describe cell rear velocity as a function of applied or internal forces is given elsewhere (Décavé et al., 2002b). The solid line relating the front speed to the applied shear stress is hand-drawn.