Figure 1.

Hybrid model of cell spreading regulated by integrin signaling. (A) The signaling network shows the flow of biochemical information from the binding of fibronectin to integrin to the activation of Arp2/3, gelsolin, and G-ATP-actin. (B) The algorithm from the stochastic spatiotemporal spreading model was modified to accept a text file with the temporal concentration profile as input. At every time step in the iteration, the concentration is updated from the text file. In most cases, the time step calculated from the Gillespie's algorithm is not a direct match with the regular intervals in the concentration profile, so the algorithm interpolates the concentration of Arp2/3, gelsolin, and G-ATP-actin at that time step. (C) Concentration profiles of Arp2/3, G-ATP-actin, and gelsolin from the compartmental deterministic signaling model. These profiles are used as input to the stochastic spatiotemporal spreading model. The concentration of Arp2/3 affects the filament branching reaction, G-ATP-actin affects the elongation reaction, and gelsolin concentration affects the capping reaction. (D) Evolution of the actin filament network and the resultant shape profiles at different times in a single simulation in response to dynamic input of the varying levels of actin regulatory proteins profiles computed by the signaling network. (i) Three-dimensional view of the full network at 1 min. (ii–iv) Magnified view of the 200 nm thick region at (ii) 1 min, (iii) 3 min, and (iv) 8 min. The surface z = 0 is shown by the tan color. Note that the filaments that protrude from outside the radius are not on the surface z = 0.