Tensed Blobs of Matter:Cytoskeletal Prestress Connects Nuclear Shape with Cell Shape

Cells are dynamic, internally tensed blobs of matter. The shape of the nucleus is increasingly recognized as a cellular mechanosensor, playing a pivotal role in regulating chromatin organization and gene expression in response to mechanical cues. Yet a lack of quantitative understanding of how the cell’s internal scaffolding influences the structural relationship between cell and its nucleus remains. Here, we address this fundamental question by examining how cytoskeletal prestress influences the relationship between cell and nuclear morphology using a morphomics approach. We hypothesize that the actin cytoskeleton holds nuclear morphology in a state of prestress that follows predictably from cellular contours. To test this hypothesis, we captured high-resolution images of individual cells after cytoskeletal perturbations using pharmacological agents. Through correlation and regression analysis we measured the strength and manner of the relationship between cell and nuclear form. Our findings [1] reveal that several nuclear size features are predicted well by cellular features, and disruption of cytoskeletal prestress resulted in an altered cell-nucleus relationship. Additionally, results suggest cytoskeletal prestress modulates nuclear morphology in a non-linear manner.