Figure 3.

Contributions of soluble MMPs and MT1-MMP to ECM degradation and invadopodia speed. (A) ECM degradation by soluble MMPs (red) and MT1-MMP (blue) for three different soluble MMP secretion rates, i.e., ${\lambda }_{\text{MMP}}$ = 0.01, 0.1, and 0.5 s⁻¹. At least 50 simulations per condition were performed. Error bars are ± standard deviation. (B and C) Percentage drop in ECM degradation (B) and invadopodia speed (C) upon inhibition of soluble MMPs, i.e., upon setting ${\lambda }_{\text{MMP}}=$ 0. (D) Representative confocal z-stack immunostained images (in YZ plane) of DMSO and SB-3CT-treated MDA-MB-231 cancer cells cultured on 5.0% gelatin in the presence of 1 μM Y-27632. For localization of invadopodia, colocalized immunostained images of MT1-MMP and F-actin ($\ge$0.5 μm wide) inside the fluorescent gelatin matrix were considered as invadopodia. Scale bar represents 5 μm. (E) Representative intensity profiles of MT1-MMP/F-actin/gelatin obtained from the zoomed images shown in insets (region of interest). Gray zone indicates the location of the degraded gelatin matrix in DMSO-treated MDA-MB-231 cancer cells. (F) Quantification of percentage degradation/cell in Y-27632-treated MDA-MB-231 cancer cells seeded on 5% gelatin in the presence of DMSO and SB-3CT. Statistical significance was performed using one-way ANOVA ($n=2$, 25–30 cells per condition; ^∗∗∗p < 0.001). Error bars show mean ± SE. To see this figure in color, go online.