Matrix-Bound PAI-1 Supports Cell Blebbing via RhoA/ROCK1 Signaling
Figure 5
Modeling PAI-1 deposition and simulation of its possible effects on amoeboid cell behavior.
(A) Cellular-automata simulation of PAI-1 secretion, diffusion and deposition (vertical axis) in tumors of different cell size (10, 100 and 500 cells). (B) Detection of endogenous PAI-1 and recombinant PAI-1 14-1b by immunoblotting in SW620 cells seeded on PAI-1 14-1b at different time-points. Signal intensities were normalized to the expression of β-Tubulin. (C) Mathematical modeling of the possible effects of changes in the concentration of matrix-bound PAI-1 in the hysteretic cycle between amoeboid and mesenchymal behavior. (D) Amoeboid pseudopodal migration of a blebbing SW620 cell seeded on PAI-1 14-1b (17 h after seeding). Arrowhead indicates a pseudopod. Speed was evaluated at 0.4 µm/min (see also Video S6). (E) Transition between blebbing and spindle-shaped morphology, and back, in blebbing morphology in a SW620 cell (★) seeded on PAI-1 14-1b (7 h after seeding) (see also Video S7). Bar, 10 µm.