A Mathematical Model of T Lymphocyte Calcium Dynamics Derived from Single Transmembrane Protein Properties
نویسندگان
چکیده
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.
منابع مشابه
Molecular Insight into the Mutual Interactions of Two Transmembrane Domains of Human Glycine Receptor (TM23-GlyR), with the Lipid Bilayers
Appearing as a computational microscope, MD simulation can ‘zoom in’ to atomic resolution to assess detailed interactions of a membrane protein with its surrounding lipids, which play important roles in the stability and function of such proteins. This study has employed the molecular dynamics (MD) simulations, to determine the effect of added DMPC or DMTAP molecules on the structure of D...
متن کاملKlotho as a Novel Cardioprotective Protein in Aged Heart
In recent years, researchers have been looking for genes whose products can directly affect the aging process. Among these, the anti-aging protein klotho has attracted much attention. This single transmembrane protein is expressed in the renal tissues, parathyroid gland and choroid network of the brain and acts as a co-receptor for Fibroblast Growth Factor FGF. In this way, it contributes to c...
متن کاملEstimation of the Elastic Properties of Important Calcium Silicate Hydrates in Nano Scale - a Molecular Dynamics Approach
Approximately, 50 to 70 percent of hydration products in hydrated cement paste are polymorphisms of C-S-H gel. It is highly influential in the final properties of hardened cement paste. Distinguishing C-S-H nano-structure significantly leads to determine its macro scale ensemble properties. This paper is dealt with nano-scale modeling. To achieve this, the most important C-S-H compounds, with a...
متن کاملThe analysis of a disease-free equilibrium of Hepatitis B model
In this paper we study the dynamics of Hepatitis B virus (HBV) infection under administration of a vaccine and treatment, where the disease is transmitted directly from the parents to the offspring and also through contact with infective individuals. Stability of the disease-free steady state is investigated. The basic reproductive rate, $R_0$, is derived. The results show that the dynamics of...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 4 شماره
صفحات -
تاریخ انتشار 2013