Quantifying intermittent transport in cell cytoplasm

Active cellular transport is a fundamental mechanism for protein and vesicle delivery, cell cycle and molecular degradation. Viruses can hijack the transport system and use it to reach the nucleus. Most transport processes consist of intermittent dynamics, where the motion of a particle, such as a virus, alternates between pure Brownian and directed movement along microtubules. In this communication, we estimate the mean time for particle to attach to a microtubule network. This computation leads to a coarse grained equation of the intermittent motion in radial and cylindrical geometries. Finally, by using the degradation activity inside the cytoplasm, we obtain refined asymptotic estimations for the probability and the mean time a virus reaches a small nuclear pore.Comment: 4 pages, 5 figures accepted as rapid communication in Phys. Rev.

Shigella Effector IpaB-Induced Cholesterol Relocation Disrupts the Golgi Complex and Recycling Network to Inhibit Host Cell Secretion

Shigella infection causes destruction of the human colonic epithelial barrier. The Golgi network and recycling endosomes are essential for maintaining epithelial barrier function. Here we show that Shigella epithelial invasion induces fragmentation of the Golgi complex with consequent inhibition of both secretion and retrograde transport in the infected host cell. Shigella induces tubulation of the Rab11-positive compartment, thereby affecting cell surface receptor recycling. The molecular process underlying the observed damage to the Golgi complex and receptor recycling is a massive redistribution of plasma membrane cholesterol to the sites of Shigella entry. IpaB, a virulence factor of Shigella that is known to bind cholesterol, is necessary and sufficient to induce Golgi fragmentation and reorganization of the recycling compartment. Shigella infection-induced Golgi disorganization was also observed in vivo, suggesting that this mechanism affecting the sorting of cell surface molecules likely contributes to host epithelial barrier disruption associated with Shigella pathogenesis

Extended Narrow Escape with Many Windows for Analyzing Viral Entry into the Cell Nucleus

International audienceMany viruses must enter the cell nucleus through small nanopores in order to replicate. We model here the viral motion as a stochastic process described by the Survival Fokker-Planck equation. We estimate the probability and the conditional mean first passage time that a viral trajectory is absorbed at a small nuclear pore before being terminated. The method is based on the explicit Neumann-Green's function. The cell nucleus is modeled as a three dimensional ball, covered with thousands of small absorbing windows. The minimum distance between them defines the smallest spatial scale that is an unavoidable limit for efficient stochastic simulations. Derived asymptotic formula agree with stochastic simulations and reveal how small and large geometrical parameters define the cytoplasmic stage of viral infection

Modeling the early steps of viral infection (a stochastic approach)

PARIS-BIUSJ-Mathématiques rech (751052111) / SudocSudocFranceF

Electrodiffusion models of synaptic potentials in dendritic spines

International audienceThe biophysical properties of dendritic spines play a critical role in neuronal integration but are still poorly understood, due to experimental difficulties in accessing them. Spine biophysics has been traditionally explored using computational models based on cable theory. However, cable theory ignores electrodiffusion (i.e. the interaction between electric fields and ionic diffusion) as it assumes that concentration changes associated with ionic currents are negligible. This assumption, while true for large neuronal compartments, could be incorrect when applied to some femto-liter size structures such as dendritic spines. To explore this, we use here the Poisson (P) and Nernst-Planck (NP) equations, which relate electric field to charge and Fick's law of diffusion, to model ion concentration dynamics in spines receiving excitatory synaptic potentials (EPSPs). We use experimentally measured voltage transients from spines with nanoelectrodes to explore these dynamics with realistic parameters. We find that (i) passive diffusion and electrodiffusion jointly affect the kinetics of spine EPSPs; (ii) spine geometry plays a key role in shaping EPSPs; and, (iii) the spine-neck resistance dynamically decreases during EPSPs, leading to short-term synaptic facilitation. Our formulation, which complements and extends cable theory, can be easily adapted to model ionic biophysics in other nanoscale bio-compartments