Published on Thu Sep 30 2021

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

Wang, W., Poe, D., Yang, Y., Hyatt, T., Xing, J.

Transition path sampling and transition path theory focus on an ensemble of trajectories that connect the initial and final states in a state space. It is generally unfeasible to experimentally observe these trajectories in multiple dimensions and compare to theoretical results.

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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. 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. 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-{beta} 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.