Abstract
The nuclear pore complex (NPC) is the unique gateway to the cell nucleus and is primarily filled with intrinsically disordered proteins (IDPs) rich in Phe-Gly (FG) repeat domains. While the microdynamics of these IDPs is still under debate, there is no information and/or consensus about their microrheological properties. Here, we use state-of-the-art computational methods to explore, for the first time, the microrheology of IDPs confined inside the nuclear pore. Our results indicate that the IDPs rich in FG repeat domains show an intriguing rheological behavior, which uniquely stems from the interplay of biophysical factors including hydrophobicity, charge, the ratios of positive and negative charge content to hydrophobicity content, geometrical confinement, chains’ lengths, channel wall permeability, and the chains’ end-tethering. Performing several long-run biophysical simulations of tens of milliseconds, we developed detailed mechanical spectrums of the polymeric meshwork inside the NPC under these physical conditions over a wide range of frequencies. It appears that among these factors, the chains’ end-tethering plays the dominant role in shaping the mechanical spectrum of FG-meshwork, particularly in the low-frequency regime. The frequency-dependent viscosity of the FG-meshwork is reminiscent of pseudo-plasticity, and thus, the FG-repeats form a shear-thinning polymeric meshwork. The meshwork poses a ‘super-viscous’ environment to the inert (non-specific) cargos while behaving as a less viscous liquid for nuclear-transport-factor-bound cargos.
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