Flow & Transport in the Cytoskeleton
The cytoskeleton is a highly dynamic network of filaments permeated by the cell cytoplasm. The cytoskeletal filaments are continuously moved by forces from nanoscopic motors that attach to and walk along them. These movements within the cell generate flows that are on the scale of the cell. These induced fluid-structures (filaments) interactions are the cell’s self-organized structures and their mechanical response; yet they have been largely ignored in previous studies. The purpose of this research direction is to use computer simulations and mathematical modeling to understand the role of fluid-structure interactions and cellular flows on the cytoskeleton organization and mechanics.
Positioning of the mitotic spindle: In collaboration with Shelly’s group (NYU, and Flatiron Institute) and Needleman Lab (Harvard) we have studied the positioning of mitotic spindle during the first cell division in C. elegans under different force generation models. We find that each force model produces a different signature in its induced cytoplasmic flow. By comparing the simulated flows with the measured ones we were able to show that spindle positioning throughout cell division is dominated by pulling forces from dynein motors at the cell cortex.
The interplay between chromatin mechanics and chromosome movement during cell division: During metaphase in cell division, chromosomes are under tensile stresses generated by active interactions of the microtubules within the mitotic spindle with a disk-like protein assembly on the chromosomes known as the kinetochore. There have been many studies on the structure of kinetochore, proteins involved and its mechanical interactions with microtubules. But we know much less about the effect of chromatin structure that connects the kinetochores of sister chromosomes. We seek to answer this question in a collaboration with the Labs of P. Maddox and K. Bloom (UNC, Biology). Our tools are simple toy models, single molecule imaging, fluorescent microscopy and genetic perturbation. We use chromosome deformations, oscillations and correlated motions as mechanical readouts.
Collaborators:
Shelley’s group (Courant Institute, NYU & Flatiron Institute, Simons Foundation)
The Needleman Lab (SEAS and Biology, Harvard University)
The Lab of P. Maddox (Biology, UNC-CH)
The Bloom Lab (Biology, UNC-CH)
Related publications:
Wu, H. Y., Kabacaoğlu, G., Nazockdast, E., Chang, H. C., Shelley, M. J., & Needleman, D. J. (2024). Laser ablation and fluid flows reveal the mechanism behind spindle and centrosome positioning. Nature Physics, 20(1), 157-168.
Nazockdast, E. (2019). Hydrodynamic interactions of filaments polymerizing against obstacles. Cytoskeleton, 76(11-12), 586-599.
Du Roure, O., Lindner, A., Nazockdast, E. N., & Shelley, M. J. (2019). Dynamics of flexible fibers in viscous flows and fluids. Annual Review of Fluid Mechanics, 51, 539-572.
Nazockdast, E., Rahimian, A., Needleman, D., & Shelley, M. (2017). Cytoplasmic flows as signatures for the mechanics of mitotic positioning. Molecular biology of the cell, 28(23), 3261-3270.
Nazockdast, E., Rahimian, A., Zorin, D., & Shelley, M. (2017). A fast platform for simulating semi-flexible fiber suspensions applied to cell mechanics. Journal of Computational Physics, 329, 173-209.
