Spatial Modeling and Simulation of Diffusion in Nuclei of Living Cells
The mobility of fluorescently labelled molecules in the interphase nucleus has been increasingly employed to investigate the spatial organization of the interchromosomal space. We suggest an improved two-dimensional anisotropic diffusion model to address the inhomogeneous nature of nuclear organization, which is at odds with the generally applied ’well-mixed’ compartmental assumption. To consider the transfer function of the imaging system, we derived a modified fundamental solution of the two-dimensional, time-dependent diffusion equation. The model was validated through comparison of the forward simulation results with fluorescence recovery after photobleaching experiments using nuclear localization signal (NLS) – tagged YFP recorded by confocal laser scanning microscopy. To improve the fit error in the vicinity of the nuclear boundary, we suggest an isotropic diffusion model with Neumann boundary condition accounting for the exact shape of the nuclear boundary. The suggested approach is a first step towards diffusion tomography of the cell nucleus.
KeywordsFundamental Solution Nuclear Localization Signal Spatial Modeling Fluorescence Recovery After Photobleaching Chromosome Territory
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