Boolean modeling of mechanosensitive epithelial to mesenchymal transition and its reversal.

ABSTRACT: The significance of biophysical modulators of the epithelial to mesenchymal transition (EMT) is demonstrated by experiments that document full EMT on stiff, nano-patterned substrates in the absence of biochemical induction. Yet, current models focus on biochemical triggers of EMT without addressing its mechanosensitive nature. Here, we built a Boolean model of EMT triggered by mechanosensing - mitogen crosstalk. Our model reproduces epithelial, hybrid E/M and mesenchymal phenotypes, the role of autocrine TGFβ signaling in maintaining mesenchymal cells in the absence of external drivers, inhibition of proliferation by TGFβ, and its apoptotic effects on soft ECM. We offer testable predictions on the density-dependence of partial EMT, its molecular drivers, and the conflict between mitosis an

SUBMITTER: Sullivan E 

PROVIDER: S-EPMC10030917 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature