Probing the Functional Integration of Mechanical Signals to Cell Nucleus

Abstract

For cells to adapt to different tissues and changes in tissue mechanics, they must be able to respond to mechanical cues by changing gene expression patterns. These responses potentially involve major changes in nuclear organization and structure to reflect epigenetic changes in the nucleus. However, it is unclear how physical cues received at the plasma membrane integrate to the functional architecture of the cell nucleus. To probe this, we applied mechanical forces through magnetic particles adhered to the plasma membrane of single cells and mapped accompanying changes in cytoskeletal reorganization, soluble signalling intermediates, nuclear morphology and chromatin remodelling using high resolution fluorescence anisotropy imaging. Application of force on the plasma membrane resulted in spatio-temporal reorganization of actin cytoskeleton and chromatin assembly and the translocation of transcription co-factor Megakaryoblastic acute leukemia factor (MKL) from the cytoplasm to the nucleus. Taken together our results evidence a strong architectural coupling between physico-chemical networks and spatial organization of the chromosomes within the nucleus facilitating mechanotransduction.