Mechanotransdcution of epithelial density: from cell adhesions to the nucleus

In multicellular organisms, the perception of cell density within a cohesive tissue is thought to underlie the regulation of tissue growth, homeostasis and regeneration. However, the mechanisms by which cells sense and adapt their behaviour to their density within the tissue remain largely unknown.
To address this question, we used genetically encoded biosensors of protein mechanics and enzymatic activity, genetic and pharmacological perturbations, and quantitative fluorescence microscopy on cultured model epithelia to study mechanotransduction pathways downstream of cell density.  
We found that epithelial cells respond to density by integrating a combination of force-gated enzymatic activations and protein translocations that occur in cell adhesion complexes and at the nuclear envelope. Ultimately, chemical and mechanical signals converge into a nuclear mechanotransduction pathway that controls cell migration and may also coordinate nuclear activities across the tissue.