Predicting YAP/TAZ nuclear translocation in response to ECM mechanosensing

Area of Science:

• Cell Biology
• Biophysics
• Biomaterials Science

Background:

• Cells perceive mechanical signals from the extracellular matrix (ECM) through mechanotransduction pathways.
• Nuclear translocation of YAP/TAZ proteins is a key outcome of ECM mechanosensing.
• Previous models focused on linear elastic ECM, limiting scope.

Purpose of the Study:

• To extend computational models of nuclear mechanotransduction to include complex ECM behaviors.
• To investigate YAP/TAZ translocation dynamics influenced by nuclear deformation.
• To unify understanding of diverse cell mechanosensing responses.

Main Methods:

• Development of an extended computational model incorporating viscosity, viscoelasticity, and viscoplasticity of the ECM.
• Detailed simulation of YAP/TAZ translocation dynamics based on nuclear deformation.
• Validation against diverse cellular mechanosensing responses.

Main Results:

• The extended model accurately predicts mechanosensing responses across various cell types.
• ECM properties like viscosity significantly influence YAP/TAZ nuclear accumulation.
• Nuclear deformation is a critical mediator in the YAP/TAZ translocation pathway.

Conclusions:

• Diverse cellular mechanosensing phenomena can be explained by a unified set of pathways.
• The model provides a predictive framework for understanding cell-ECM interactions.
• This research advances the understanding of how mechanical cues regulate gene expression via YAP/TAZ.