Modeling compartmentalization within intracellular signaling pathway

\nWe present a novel approach to modeling receptor-activated signaling pathways that take into account the compartmentalization of receptors and their effectors, both on the cell surface and in dynamic intracellular vesicles called endosomes. The first building block of the model concerns compartment dynamics. It takes into account creation of de novo endosomes, i.e. endocytosis, and further recycling of endosomes to the cell surface or degradation, as well as fusion of endosomes via coagulation dynamics. The second building block concerns biochemical reactions on the cell surface and within intra-cellular compartments. Both building blocks are coupled by the transfer of molecules that occurs at each event that modifies the compartments.\nThe model is formulated as a integro-partial differential equation, with transport and coagulation operators, and source terms, coupled to an integro-differential equation. In this work, we prove sufficient conditions to obtain exponential ergodicity for the size distribution of intracellular compartments. We further design a finite volume scheme to simulate our model. Finally, we show two application cases that show qualitative agreement with recently published data, proving that our model can help capture the spatio-temporal complexity of receptor-activated signaling pathway.\n

Publication Details

Journal
Springer Link (Chiba Institute of Technology)
Published
2024-11-18
DOI
https://doi.org/10.1051/proc/202477100/pdf
Primary Topic
Gene Regulatory Network Analysis
Type
article
Field-Weighted Citation Impact
0.00

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article

Modeling compartmentalization within intracellular signaling pathway

Springer Link (Chiba Institute of Technology)
Gene Regulatory Network Analysis
article

Modeling compartmentalization within intracellular signaling pathway

article en

Abstract

\nWe present a novel approach to modeling receptor-activated signaling pathways that take into account the compartmentalization of receptors and their effectors, both on the cell surface and in dynamic intracellular vesicles called endosomes. The first building block of the model concerns compartment dynamics. It takes into account creation of de novo endosomes, i.e. endocytosis, and further recycling of endosomes to the cell surface or degradation, as well as fusion of endosomes via coagulation dynamics. The second building block concerns biochemical reactions on the cell surface and within intra-cellular compartments. Both building blocks are coupled by the transfer of molecules that occurs at each event that modifies the compartments.\nThe model is formulated as a integro-partial differential equation, with transport and coagulation operators, and source terms, coupled to an integro-differential equation. In this work, we prove sufficient conditions to obtain exponential ergodicity for the size distribution of intracellular compartments. We further design a finite volume scheme to simulate our model. Finally, we show two application cases that show qualitative agreement with recently published data, proving that our model can help capture the spatio-temporal complexity of receptor-activated signaling pathway.\n

Springer Link (Chiba Institute of Technology)
Dipartimenti di Eccellenza, Agence Nationale de la Recherche, Ministero dell’Istruzione, dell’Università e della Ricerca, Junta de Andalucía, Nature, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, European Regional Development Fund
Openalex Percentile: Top 73%
Gene Regulatory Network Analysis
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Modeling compartmentalization within intracellular signaling pathway · Springer Link (Chiba Institute of Technology) (2024) | TGRS Research Map | TGRS