A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties.
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Authors
Schmeitz, ChristineHernandez-Vargas, Esteban Abelardo
Fliegert, Ralf
Guse, Andreas H
Meyer-Hermann, Michael
Issue Date
2013
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Show full item recordAbstract
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.Citation
A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties. 2013, 4:277 Front ImmunolAffiliation
Department of Systems Immunology, Helmholtz Centre for Infection Research , Braunschweig , Germany.Journal
Frontiers in immunologyPubMed ID
24065966Type
ArticleLanguage
enISSN
1664-3224ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2013.00277
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