(26c) Measuring Changes in Cell Mechanics and Nuclear Rheology Associated with Cellular Transitions in Monolayers Associated with Development

The nucleus contains the genome and all of the regulatory proteins required for gene expression. However, gene expression changes drastically between different cell types, during development and differentiation, and during phenotypic switches within a cell. Also, mechanical cues are implicated in a diverse field of cellular processes including differentiation and during phenotypic switches. We aim to understand the mechanisms by which force transmission from the extracellular environment are interpreted by cells as changes in gene expression, particularly related to development. We are working in developing advanced tools for imaging forces and force propagation within cells and tissues using numerous sensor systems. We use Sensors from Nuclear Kinetics (SINK), particle tracking that correlates that chromatin fluctuations and nuclear rheology with force transmission throughout the cell. We then couple these measurements with traction force microscopy (TFM) and FRET-tension sensors to get a complete measure of force throughout cells, between cell-cell contacts, and between cells and the extracellular matrix. We use these complementary tools to examine cells in mature epithelial monolayers, as well as in epithelial monolayers that are undergoing epithelial to mesenchymal transitions, and cells on altered substrates. By using nuclear rheology as one of the readouts it allows us to examine both cellular forces and changes in gene expression and movement of transcriptionally active domains and heterochromatin domains.