Fig. 9. Hypothetical model suggesting the involvement of a switch between phosphorylated and non-phosphorylated paxillin and a negative feedback loop with FAK in the regulation of adhesion dynamics. (A) Based on the results in this paper we constructed a working model composed of the following assumptions: (1) Phosphopaxillin is initially recruited following an external stimuli (integrin adhesion). (2) Thereafter its recruitment rate is positively regulated by the existence of both phosphopaxillin and paxillin. (3) FAK recruitment into the adhesion is dependent on phosphopaxillin concentration. (4) Phosphopaxillin disassembles in a FAK-dependent manner where FAK concentration increases the disassembly rate. (5) FAK disassembly occurs at the same rate it assembles, after a short delay. (6) Phosphopaxillin becomes dephosphorylated at a high rate when mechanical force exists and paxillin becomes phosphorylated constantly at a low rate. (7) Paxillin disassembles at a constant rate. (B) The above assumptions were compiled into a set of three simple differential equations (see model in Materials and Methods) and their solutions for the changing concentration of phosphopaxillin (red), FAK (green) and paxillin (blue) are given here in graphical form. Arrows under the time line mark the adhesion stimuli. Gray shading depicts the existence of mechanical force. The change over time in adhesion `area' (sum of paxillin and phosphopaxillin) is presented in the insert. (C) This hypothetical scheme presents the manner by which a paxillin phosphorylation switch and FAK might regulate the formation of the three integrin-mediated adhesion forms: focal complexes (FX), focal adhesions (FA) and fibrillar adhesions (FB).