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Stéphanie Portet

Publications and source records attributed to Stéphanie Portet.

3 recordsLinked to original sources

Within-host immunology to age-of-infection epidemiology via a virtual cohort

We present a methodology providing a one-directional link from within-host individual heterogeneity to population-level disease transmission dynamics. The methodology works in several steps. A within-host model is investigated numerically to determine pathogen and immunological parameters leading to the largest variation of model responses. These key parameters are used to generate a synthetic population of individuals whose temporal immunological response profiles are recorded. These responses are ranked in terms of the severity of experienced outcomes, from mild infections to death, as a function of time since infection. This is used to parametrise an age-of-infection structured epidemiological model to study the transmission dynamics of the disease at the population level. The approach is illustrated using a within-host model describing SARS-CoV-2 infection and an SIR population-level model.

q-bio.PE↗

Models of Vimentin Organization Under Actin-Driven Transport

Intermediate filaments form an essential structural network, spread throughout the cytoplasm and play a key role in cell mechanics, intracellular organization and molecular signaling. The maintenance of the network and its adaptation to the cell's dynamic behavior relies on several mechanisms implicating cytoskeletal crosstalk which are not fully understood. Mathematical modeling allows us to compare several biologically realistic scenarios to help us interpret experimental data. In this study, we observe and model the dynamics of the vimentin intermediate filaments in single glial cells seeded on circular micropatterns following microtubule disruption by nocodazole treatment. In these conditions, the vimentin filaments move towards the cell center and accumulate before eventually reaching a steady-state. In absence of microtubule-driven transport, the motion of the vimentin network is primarily driven by actin-related mechanisms. To model these experimental findings, we hypothesize that vimentin may exist in two states, mobile and immobile, and switches between the states at unknown (either constant or non-constant) rates. Mobile vimentin are assumed to advect with either constant or non-constant velocity. We introduce several biologically realistic scenarios using this set of assumptions. For each scenario, we use differential evolution to find the best parameter sets resulting in a solution that most closely matches the experimental data, then the assumptions are evaluated using the Akaike Information Criterion. This modeling approach allows us to conclude that our experimental data are best explained by a spatially dependent trapping of intermediate filaments or a spatially dependent speed of actin-dependent transport.

q-bio.SC↗

A coupled bulk-surface model for cell polarisation

Several cellular activities, such as directed cell migration, are coordinated by an intricate network of biochemical reactions which lead to a polarised state of the cell, in which cellular symmetry is broken, causing the cell to have a well defined front and back. Recent work on balancing biological complexity with mathematical tractability resulted in the proposal and formulation of a famous minimal model for cell polarisation, known as the wave pinning model. In this study, we present a three-dimensional generalisation of this mathematical framework through the maturing theory of coupled bulk-surface semilinear partial differential equations in which protein compartmentalisation becomes natural. We show how a local perturbation over the surface can trigger propagating reactions, eventually stopped in a stable profile by the interplay with the bulk component. We describe the behavior of the model through asymptotic and local perturbation analysis, in which the role of the geometry is investigated. The bulk-surface finite element method is used to generate numerical simulations over simple and complex geometries, which confirm our analysis, showing pattern formation due to propagation and pinning dynamics. The generality of our mathematical and computational framework allows to study more complex biochemical reactions and biomechanical properties associated with cell polarisation in multi-dimensions.

q-bio.CB↗