Predicting TGF-β-Induced Epithelial-Mesenchymal Transition using Data Assimilation

Abstract

conformation. Vesicles where fluorescence photobleached in a single-step were identified as containing single protomers. These traces were either dynamic (fluorescence fluctuated between two states) or nondynamic (no fluctuations). The fraction of protomers that showed dynamic behavior increased saturably with ATP from $40% at 0 ATP to $70% at 1 mM (saturating) ATP. This titration curve could not be fitted with a single binding isotherm. A fit to a model that assumed a heterogeneous mixture of pump molecules with high-and low-affinity ATP binding showed: (a) high-and low-affinity apparent dissociation constants of 0.1 and 40 mM; and (b) that the preparation had equal amounts of high-and low-affinity forms of the pump. Our data suggest that binding heterogeneity is an intrinsic property of the protomer and is not attributable to aggregation.

Computational models to explore the complexity of the epithelial to mesenchymal transition in cancer

“…Indeed, it has been shown to spark a virtuous circle in which both the model and the experimental study are improved through the integration of relevant information. As an example, data assimilation has recently been applied to the prediction of transition timing in EMT (Mendez, Hoffman, Cherry, Lemmon, & Weinberg, 2019). In the latter method, experimental observations and model predictions are iteratively combined to provide a more accurate description of both the observed and unobserved characteristics of the system.…”