Epithelial-to-mesenchymal transition proceeds through directional destabilization of multidimensional attractor

Abstract

A problem ubiquitous in almost all scientific areas is escape from a metastable state, or relaxation from one stationary distribution to a new one 1 . More than a century of studies lead to celebrated theoretical and computational developments such as the transition state theory and reactive flux formulation. Modern transition path sampling and transition path theory focus on an ensemble of trajectories that connect the initial and final states in a state space 2, 3 . However, it is generally unfeasible to experimentally observe these trajectories in multiple dimensions and compare to theoretical results. Here we report and analyze single cell trajectories of human A549 cells undergoing TGF-β induced epithelial-to-mesenchymal transition (EMT) in a combined morphology and protein texture space obtained through time lapse imaging. From the trajectories we identify parallel reaction paths with corresponding reaction coordinates and quasi-potentials. Studying cell phenotypic transition dynamics will provide testing grounds for nonequilibrium reaction rate theories. AUTHOR CONTRIBUTIONSJ. X. designed the research; W. W. and J. X. performed the research and wrote the paper. SUPPLEMENTAL FIGURE CAPTIONFigure S1 Different views of the trajectory shown in Fig. 2E. (A) Representation in the Morphology PC1-Vimentin Haralick PC1 space. (B) Representation in the Vimentin Haralick PC3-Vimentin Haralick PC4 space.Figure S2 Iterative procedure of the finite temperature string method. (A) Flow chart of the procedure. (B) Example RC curves obtained at different iteration cycle.

Minimal frustration underlies the usefulness of incomplete regulatory network models in biology

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Comparative single-cell transcriptomes of dose and time dependent epithelial-mesenchymal spectrums

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A plausible accelerating function of intermediate states in cancer metastasis

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