Effects of Cell Contractility on Dynamic Movement of YAP in Living Cells
Newsha Koushki
Dynamic YAP localization in contractile 3T3 cells. a) example images of EBFP-nuclei with EGFP-YAP and immunofluorescently labeled endogenous YAP demonstrate that exogenous and endogenous YAP are both found principally in the cytoplasm (YR = YAP nuclear to cytoplasmic ratio, YR < 1 YAP in cytoplasm, YR > 1.5 YAP in nucleus. b) YAP nuclear localization (YR) is dynamic in time, and uncorrelated with substrate stiffness (color depicts substrate modulus). c) YR is correlated with cell contractile work across all investigated substrate stiffness(color depicts substrate modulus). d) YR is inversely correlated with nuclear volume, with intact or inhibited cytoskeleton.
The detailed mechanobiology of how cells biochemically transduce mechanical signals is reshaping our basic understanding of life and pathology. In particular, Yes Associated Protein (YAP) has emerged as a key mechanosensitive transcriptional factor in diverse organisms, and quite broadly in human development and pathology. In our research, we employ a variety of biophysical approaches to present a comprehensive analysis of the relationship between cell contractility, nuclear deformation, Lamin A localization, and YAP nuclear translocation. We have found that nuclear deformation from LINC-mediated cytoskeletal contractility or extracellular osmotic forces triggers YAP nuclear localization. By modulating the expression of lamin A and nuclear stiffness, we find that nuclear rigidity modulates deformation-mediated YAP nuclear localization.
McGill University is located on land which has long served as a site of meeting and exchange amongst Indigenous peoples. We honor, recognize, and respect these nations as the traditional stewards of the lands and waters on which we meet today.
McConnell Engineering Building
3480 University Street, Room 350
Montreal, Quebec H3A 2A7
Phone: 514-714-8239
Fax: 514-398-7379
Email: allen.ehrlicher@mcgill.ca
Office: McConnell Engineering Building 358