Predicting YAP/TAZ nuclear translocation in response to ECM mechanosensing

Bo Cheng, Moxiao Li, Wanting Wan, Hui Guo, Guy M. Genin, Min Lin, Feng Xu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cells translate mechanical cues from the extracellular matrix (ECM) into signaling that can affect the nucleus. One pathway by which such nuclear mechanotransduction occurs is a signaling axis that begins with integrin-ECM bonds and continues through a cascade of chemical reactions and structural changes that lead to nuclear translocation of YAP/TAZ. This signaling axis is self-reinforcing, with stiff ECM promoting integrin binding and thus facilitating polymerization and tension in the cytoskeletal contractile apparatus, which can compress nuclei, open nuclear pore channels, and enhance nuclear accumulation of YAP/TAZ. We previously developed a computational model of this mechanosensing axis for the linear elastic ECM by assuming that there is a linear relationship between the nucleocytoplasmic ratio of YAP/TAZ and nuclear flattening. Here, we extended our previous model to more general ECM behaviors (e.g., viscosity, viscoelasticity, and viscoplasticity) and included detailed YAP/TAZ translocation dynamics based on nuclear deformation. This model was predictive of diverse mechanosensing responses in a broad range of cells. Results support the hypothesis that diverse mechanosensing phenomena across many cell types arise from a simple, unified set of mechanosensing pathways.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalBiophysical Journal
Volume122
Issue number1
DOIs
StatePublished - Jan 3 2023

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