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Register a new userHeterogeneous anomalous diffusion of virus in cytoplasm of a living cell
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Yuichi Itto
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The infection pathway of virus in cytoplasm of a living cell is studied from the viewpoint of diffusion theory. The cytoplasm plays a role of a medium for stochastic motion of the virus contained in the endosome as well as the free virus. It is experimentally known that the exponent of anomalous diffusion fluctuates in localized areas of the cytoplasm. Here, generalizing fractional kinetic theory, such fluctuations are described in terms of the exponent locally distributed over the cytoplasm, and a theoretical proposition is presented for its statistical form. The proposed fluctuations may be examined in an experiment of heterogeneous diffusion in the infection pathway.
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In their work [Proc. Natl. Acad. Sci. USA 112 (2015) E5725], Bosse et al. experimentally showed that virus capsid exhibits not only normal diffusion but also anomalous diffusion in nucleus of a living cell. There, it was found that the distribution of fluctuations of the diffusion exponent characterizing them takes the Gaussian form, which is, quite remarkably, the same form for two different types of the virus. This suggests high robustness of such fluctuations. Here, the statistical property of local fluctuations of the diffusion exponent of the virus capsid in the nucleus is studied. A maximum-entropy-principle approach (originally proposed for a different virus in a different cell) is applied for obtaining the fluctuation distribution of the exponent. Largeness of the number of blocks identified with local areas of interchromatin corrals is also examined based on the experimental data. It is shown that the Gaussian distribution of the local fluctuations can be derived, in accordance with the above form. In addition, it is quantified how the fluctuation distribution on a long time scale is different from the Gaussian distribution.
Diffusion of tracer particles in the cytoplasm of mammalian cells is often anomalous with a marked heterogeneity even within individual particle trajectories. Despite considerable efforts, the mechanisms behind these observations have remained largely elusive. To tackle this problem, we performed extensive single-particle tracking experiments on quantum dots in the cytoplasm of living mammalian cells at varying conditions. Analyses of the trajectories reveal a strong, microtubule-dependent subdiffusion with antipersistent increments and a substantial heterogeneity. Furthermore, particles stochastically switch between different mobility states, most likely due to transient associations with the cytoskeleton-shaken endoplasmic reticulum network. Comparison to simulations highlight that all experimental observations can be fully described by an intermittent fractional Brownian motion, alternating between two states of different mobility.
The exponent of anomalous diffusion of virus in cytoplasm of a living cell is experimentally known to fluctuate depending on localized areas of the cytoplasm, indicating heterogeneity of diffusion. In a recent paper (Itto, 2012), a maximum-entropy-principle approach has been developed in order to propose an Ansatz for the statistical distribution of such exponent fluctuations. Based on this approach, here the deviation of the statistical distribution of the fluctuations from the proposed one is studied from the viewpoint of Einsteins theory of fluctuations (of the thermodynamic quantities). This may present a step toward understanding the statistical property of the deviation. It is shown in a certain class of small deviations that the deviation obeys the multivariate Gaussian distribution.
Renewal-anomalous-heterogeneous files are solved. A simple file is made of Brownian hard spheres that diffuse stochastically in an effective 1D channel. Generally, Brownian files are heterogeneous: the spheres diffusion coefficients are distributed and the initial spheres density is non-uniform. In renewal-anomalous files, the distribution of waiting times for individual jumps is exponential as in Brownian files, yet obeys: {psi}_{alpha} (t)~t^(-1-{alpha}), 0<{alpha}<1. The file is renewal as all the particles attempt to jump at the same time. It is shown that the mean square displacement (MSD) in a renewal-anomalous-heterogeneous file, <r^2>, obeys, <r^2>~[<r^2>_{nrml}]^{alpha}, where <r^2 >_{nrml} is the MSD in the corresponding Brownian file. This scaling is an outcome of an exact relation (derived here) connecting probability density functions of Brownian files and renewal-anomalous files. It is also shown that non-renewal-anomalous files are slower than the corresponding renewal ones.
Virus capsids in interchromatin corrals of a cell nucleus are experimentally known to exhibit anomalous diffusion as well as normal diffusion, leading to the Gaussian distribution of the diffusion-exponent fluctuations over the corrals. Here, the sojourn-time distribution of the virus capsid in local areas of the corral, i.e., probability distribution of the sojourn time characterizing diffusion in the local areas, is examined. Such an area is regarded as a virtual cubic block, the diffusion property in which is normal or anomalous. The distribution, in which the Gaussian fluctuation is incorporated, is shown to tend to slowly decay. Then, the block-size dependence of average sojourn time is discussed. A comment is also made on (non-)Markovianity of the process of moving through the blocks.
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