RT Journal Article
SR Electronic
T1 Analyses of Multi-dimensional Single Cell Trajectories Quantify Transition Paths Between Nonequilibrium Steady States
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.27.920371
DO 10.1101/2020.01.27.920371
A1 Wang, Weikang
A1 Xing, Jianhua
YR 2020
UL http://biorxiv.org/content/early/2020/01/28/2020.01.27.920371.abstract
AB A problem ubiquitous in almost all scientific areas is escape from a metastable state, or relaxation from one stationary distribution to a new one1. 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 space2, 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.