A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties.

2.50
Hdl Handle:
http://hdl.handle.net/10033/304662
Title:
A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties.
Authors:
Schmeitz, Christine; Hernandez-Vargas, Esteban Abelardo ( 0000-0002-3645-435X ) ; Fliegert, Ralf; Guse, Andreas H; Meyer-Hermann, Michael
Abstract:
Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic, or initiates apoptosis depends on extracellular triggers and intracellular signaling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modeling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC) is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.
Affiliation:
Department of Systems Immunology, Helmholtz Centre for Infection Research , Braunschweig , Germany.
Citation:
A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties. 2013, 4:277 Front Immunol
Journal:
Frontiers in immunology
Issue Date:
2013
URI:
http://hdl.handle.net/10033/304662
DOI:
10.3389/fimmu.2013.00277
PubMed ID:
24065966
Type:
Article
Language:
en
ISSN:
1664-3224
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchmeitz, Christineen
dc.contributor.authorHernandez-Vargas, Esteban Abelardoen
dc.contributor.authorFliegert, Ralfen
dc.contributor.authorGuse, Andreas Hen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2013-10-28T15:11:25Z-
dc.date.available2013-10-28T15:11:25Z-
dc.date.issued2013-
dc.identifier.citationA mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties. 2013, 4:277 Front Immunolen
dc.identifier.issn1664-3224-
dc.identifier.pmid24065966-
dc.identifier.doi10.3389/fimmu.2013.00277-
dc.identifier.urihttp://hdl.handle.net/10033/304662-
dc.description.abstractFate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic, or initiates apoptosis depends on extracellular triggers and intracellular signaling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modeling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC) is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.en
dc.language.isoenen
dc.rightsArchived with thanks to Frontiers in immunologyen
dc.titleA mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties.en
dc.typeArticleen
dc.contributor.departmentDepartment of Systems Immunology, Helmholtz Centre for Infection Research , Braunschweig , Germany.en
dc.identifier.journalFrontiers in immunologyen

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