Title: Physical mechanisms of cell nuclear mechanics and structure
Abstract: The cell nucleus is often referred to as the “control center of the cell” because it houses the genome, which encodes cellular function. However, the nucleus is also a mechanically responsive object that actively organizes and physically protects the >1-meter-long chromatin polymer (DNA and proteins) within. To understand the physical mechanisms of these phenomena, I use simulation and theory to explore: 1) how two major nuclear components govern mechanical response and 2) how mesoscale chromosome folding is driven by molecular motors. First, I show that nuclear mechanical response is well described by a model of a polymeric shell of lamins enclosing a chromatin polymer gel. This model has two regimes of force response, which we observe experimentally. These nuclear mechanical components profoundly influence nuclear shape, particularly in human diseases such as progeria and breast cancer. Second, I develop a theory for “loop-extruding” condensin protein complexes, which compact chromosomes 1000-fold by reeling in DNA and extruding it as loops. The theory predicts that condensins with the properties recently observed in vitro cannot fully compact human chromosomes. However, the model suggests how condensins may achieve 1000-fold compaction in vivo. Together, these models illustrate how biologically essential cell-nuclear properties emerge from the mechanical response and nonequilibrium activities of chromatin.