CAREER: Fluid-structure interactions in cytoskeletal assemblies

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The cell is a mechanical machine made of smaller machines that transform chemical energy to force and motion. Cell mechanics is key to many cellular processes, including cell shape, cell motility and cell division. The main component of cell's mechanical machinery is the cytoskeleton, which is a highly dynamic network of microscopic filaments. The cytoskeletal filaments are continuously moved by forces from molecular motors that attach to and walk along them. These movements generate flows inside the cell. These induced fluid-structures (filaments) interactions are key to the cytoskeleton mechanics; yet they have been largely ignored in previous studies. The purpose of this research is to use computer simulations and mathematical modelling to develop a deep understanding of the role of fluid-structure interactions and cellular flows on the cytoskeleton organization and mechanics. The research and educational component are integrated by partnering with the Planetarium and Science Center (approximately 160,000 annual visitors) at the university, to create an immersive Virtual Reality experience so that the visitors can shrink down to the cell size and learn about cell mechanics. The team will develop a curriculum and hold workshops for high school teachers for meaningful implementation of these activities in the classroom. The cytoskeleton is a dynamic self-organized assembly of filaments - including actin filaments and microtubules - and motor-proteins immersed in the cytoplasmic fluid. The cytoskeleton is key to the cell's response to external mechanical stimuli as well as many intracellular mechanical processes, including cell motility and cell division. The nonlocal interactions between the cytoplasmic fluid and the flexible filaments are key to determining the transient structure and mechanics of the cytoskeleton. Yet these fluid-structure interactions have been largely ignored in computational studies of cytoskeletal assemblies. The principal investigator has recently developed a platform for simulating the dynamics of large assemblies of polymerizing flexible filaments in Stokes flow and their associated flows. The ultimate goal of this proposal is to use this computational platform to understand the effect of fluid-structure interactions and cytoplasmic flows on the organization and mechanics of cytoskeletal assemblies. The research is divided into three connected and complimentary Aims. The purpose of Aim 1 and Aim 2 is to develop a fundamental understanding of the role of fluid-structure interactions that is less dependent on the physiological details. This is achieved by in silico recapitulation of simplified in vitro reconstitutions of microtubule assemblies, and studying the effect of forces from motor-proteins (Aim 1), and (de)polymerization (Aim 2) on the organization and rheology of microtubule assemblies. In Aim 3, light and electron microcopy and particle tracking data is combined with simulations to study the positioning and assembly of the mitotic spindle in the first cell division of Caenorhabditis elegans.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.