Figure 6. Causal influence patterns are plastic and contextually dependent.

(A) Granger causality analysis revealed a sequence of causal interactions extending both up-stream and down-stream of Instantaneous Cell Speed (ICS): Increasing IDR [Change in CMAC Total EGFP-Paxillin intensity] per Cell (indicates per cell variation in the net rate of EGFP-Paxillin recruitment/release per CMAC) caused increased Median [EGFP-Paxillin – RubyRed-LifeAct Colocalization per CMAC] per Cell (A, left panel). Increasing Median [EGFP-Paxillin – RubyRed-LifeAct Colocalization per CMAC] per Cell caused reduced ICS (A, center panel). Increasing ICS caused increased Cell Compactness (A, right panel), indicating that fast moving cells become less round. The causal links between these four variables are summarized schematically (grey boxes), with positive and negative relationships indicated by arrows and capped lines, respectively. Analyses of Granger causality predictions for equivalent inter-feature relationships in ROCK-inhibited cells (B) reveal comparable causal relationships while Rho-activated cells did not (C). Notably, although the final causal relationship (C, right panel) was still detected, the causal effect was reversed such that increasing ICS caused decreasing Cell Compactness, i.e. increased cell speed caused cells to become more round. All variables are defined in Supporting Table S1.