Quantitative Imaging of Epithelial Cell Scattering Identifies Specific Inhibitors of Cell Motility and Cell-Cell Dissociation

Dinah Loerke, Quint le Duc, Iris Blonk, Andre Kerstens, Emma Spanjaard, Matthias Machacek, Gaudenz Danuser,* Johan de Rooij*

*To whom correspondence should be addressed. E-mail: j.derooij{at}hubrecht.eu (J.d.R.); Gaudenz_Danuser{at}hms.harvard.edu (G.D.)

This PDF file includes:

• Note S1. Phase-contrast image analysis, cell detection, and tracking.
• Note S2. Quantifying cell migration and dealing with mitotic cells.
• Note S3. Quantifying spatial dispersal using Ripley's K function.
• Note S4. Quantifying cell-cell adhesion.
• Note S5. Hierarchical clustering.
• Fig. S1. Cell tracking.
• Fig. S2. Definition of spatial dispersion parameter based on Ripley's K function.
• Fig. S3. Definition of adhesion loss parameter based on motion correlation.
• Fig. S4. Inhibition efficiency for motility, dispersal, and adhesion loss parameters.
• Fig. S5. Ranked inhibition efficiencies.
• Fig. S6. Validation of hierarchical clustering.
• Fig. S7. Velocity differences indicate adhesion specificity.
• Fig. S8. Inhibition efficiency of effective drugs on the scattering of normal and cell-cell junction-compromised MDCK cells.
• Table S1. Target names and additional information on drugs used in screen.
• References
• Legends for Movies S1 to S8

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Other Supplementary Material for this manuscript includes the following:

• Movie S1 (.mp4 format). The presence of cell-cell adhesions slows down HGF-induced cell motility.
• Movie S2 (.mov format). Motility parameter.
• Movie S3 (.mov format). Spatial dispersion parameter.
• Movie S4 (.mov format). Adhesion loss parameter.
• Movie S5 (.mp4 format). α-Catenin–depleted cells do not form functional cell-cell junctions.
• Movie S6 (.mp4 format). Knockdown of CDK1 but not CDK5 inhibits the HGF-induced increase in cell motility.
• Movie S7 (.mp4 format). Diclofenac inhibits the HGF-induced loss of cell-cell adhesion, whereas knockdown of COX-2 reduces the stability of cell-cell junctions.
• Movie S8 (.mp4 format). Blocking RSKs by chemical inhibition or siRNA-mediated knockdown inhibits the HGF-induced increase in cell motility.

© 2012 American Association for the Advancement of Science