Soft Matter Seminar: Physical mechanisms of cell nuclear mechanics and structure
Ed Banigan, Massachusetts Institute of Technology
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) contained 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 chromatin has an essential role in maintaining nuclear structure. Nuclear mechanical response is well described by a model of a chromatin polymer gel enclosed by a polymeric lamin shell. This model predicts an experimentally observable, strain-stiffening mechanical response. These mechanics lead to a buckling transition and regulate nuclear shape abnormalities found in human diseases, such as progeria and breast cancer. Second, I develop a theory for “loop-extruding” condensin protein complexes, which linearly compact chromosomes 1000-fold by reeling in DNA and extruding it as loops. While a form of this novel motor activity has been observed in recent in vitro single-molecule experiments, my theory predicts that the microscopic observations cannot fully explain in vivo human chromosome compaction. However, the model suggests how condensins may nonetheless achieve such dramatic compaction in vivo. Together, the models and corresponding experiments demonstrate how biologically essential cell-nuclear properties emerge from the mechanical response and nonequilibrium activities of chromatin.
Wednesday, December 11, 2019 at 2:30pm
Regents Hall, 351
3700 O St. NW