Individual-based models for the functional impact of signalling proteins spatial distribution and diffusion heterogeneity
type: Dataset
description: Signalling pathways allow cells to perceive and exchange information under the form of chemical signals. Such a signal generates a response of the cell through the crucial stages of reception and transduction. Different types of protein interact in a structured manner as a cascade of reactions that relay the signal from the exterior to the interior of the cell, notably through the membrane. Signalling proteins are restricted to compartments with different degrees of freedom, and diffuse either in the plasma membrane that is bidimensional interface, or in the cytoplasm which is tridimensional medium. Within these very diffusion spaces, the spatial distributions of signalling proteins are heterogeneous. The mathematical models of signalling pathways dynamics, however, classically assume that signalling proteins are distributed homogeneously. We developed computational models of biochemical reactions between populations of molecules where the state and the position of each molecule are tracked. Diffusion and reaction between simulated molecules are reproduced based on biophysically accurate stochastic processes. Such granularity allows for the reproduction of heterogeneous spatial distributions and diffusion of signalling proteins as observed in biology, and the investigation of their effect on the functioning of a simulated signalling pathway. First, we explored the effect of fixed heterogeneous receptor distributions on the extracellular ligand-receptor binding process. In simulation, receptors in clusters presented a decreased apparent affinity compared to the situation where they were distributed homogeneously. Clustering induced a redistribution of binding events that favored rebinding at short time scales at the expense of first passage binding events. Secondly, we explored the transduction stage between receptors and their membrane-bound signalling substrate at the membrane level. Clustering induced a decrease in response as well, and modified the structure of t…
issued: 2026-05-09T20:56:12.066015
language: en
modified: 2026-05-09T20:56:12.066022
contact point: Organization
  fn: CCSD
keyword: diffusion
keyword: equation-differentielle-ordinaire
keyword: individual-based-models
keyword: infoeu-reposemanticsdoctoralthesis
keyword: infoinfo-bicomputer-science-csbioinformatics-q-bioqm
keyword: marche-aleatoire
keyword: methodes-de-monte-carlo
keyword: modele-individu-centre
keyword: monte-carlo-methods
keyword: ordinary-differential-equation
keyword: random-walk
keyword: sdvbibslife-sciences-q-bioquantitative-methods-q-bioqm
keyword: signalisation
keyword: signalling
keyword: simulation
keyword: theses
landing page: https://theses.hal.science/tel-00858499

Individual-based models for the functional impact of signalling proteins spatial distribution and diffusion heterogeneity
type: Distribution
format: HTML
issued: 2026-05-09T20:56:12.078428
modified: 2026-05-09T20:56:12.047848
access URL: https://theses.hal.science/tel-00858499

test_moissonnage_selune
type: Agent