Models of the Nuclear Pore Biomechanics

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Cells in the body use many physical processes to sustain life. Many of them depend on moving large molecules into and out of the nucleus. Such transportation is done through small and complicated pathways, called nuclear pore complexes. Despite the vital importance of the nuclear pore complex in cell biology, little is known about the mechanics and dynamics of the transport of the molecules through them. This project includes fundamental research towards understanding the biomechanics of the nuclear pore complex and transport. Understanding how molecules are actively transported through these pore will ultimately inform creation of new cell-based therapeutic approaches and potentially also create industrial applications of biomimetic artificial pores. This project crosses several disciplinary boundaries including those between biology, chemistry, mechanics, and bioengineering. The multi-disciplinary approach, along with outreach targeted to underrepresented students and student teachers, will help broaden participation of underrepresented groups in research and positively impact science, technology, engineering and mathematics education. The research team will partner with the Berkeley NSF-supported BERET program to introduce the power of computational modeling to high school students.The complex, yet delicate, geometry of the nuclear pore and the fine spatiotemporal resolution at which nucleocytoplasmic transport takes place have hindered the direct, experimental investigations of this mysterious nanopore. Given the limitations of experimental techniques, computational approaches spanning multiple scales can break through to understanding by simulating its activity mechanistically. Computational models offer a strong platform for capturing the nanosecond-scale interactions between transported macromolecular cargos and the nuclear pore at nanometer spatial resolutions to examine the details of nucleocytoplasmic transport phenomena. Using a combination of bioinformatics, computational biology and biophysics modeling approaches, ranging from all-atom molecular dynamics and coarse-grained Brownian dynamics to new agent-based modeling methods, this research will shed light on the structure and function of the nuclear pore complex and the dynamics of nucleocytoplasmic traffic.