RESUMEN
This paper presents a three-dimensional finite element model for cyclic adenosine monophosphate (cAMP) signaling. Governing equations for the synthesis, diffusion, and degradation of cAMP were numerically implemented using the finite element method. Simulated results were displayed as time course plots of cAMP concentrations at selected nodes within the discretized geometry. The validity of the finite element model was assessed by comparing simulated results against analytical or other numerical solutions of cAMP concentration distribution for a spherical cellular volume. An endothelial cell was also simulated using its discretized geometry obtained from microscopic cellular cross-sectional images. Simulated solutions using the spherical cellular volume produced near identical cAMP concentration plots to the analytical solutions and were in good agreements with numerical results obtained from VCell, an existing software package for modeling cell biological systems. The validated 3-D finite element model was then employed to simulate the cAMP signaling pathway within a pulmonary microvascular endothelial cell geometry.
RESUMEN
In this work, we present a two-dimensional finite element analysis (FEA) model that describes fundamental intracellular signals of cyclic adenosine monophosphate (cAMP) in a general fashion. The model was subsequently solved numerically and the results were displayed in forms of time-course plots of cAMP concentration at a cellular location or color-filled contour maps of cAMP signal distribution within the cell at specific time points. Basic intracellular cAMP signaling was described in this model so it can be numerically validated by verifying its numerical results against available analytical solutions and against results obtained from other numerical techniques reported in the literature. This is the first important step before the model can be expanded in future work. Model simulations demonstrate that under certain conditions, sustained cAMP concentrations can be formed within endothelial cells (ECs), similar to those observed in rat pulmonary microvascular ECs. Spatial and temporal cAMP dynamic simulations indicated that the proposed FEA model is an effective tool for the study of the kinetics and spatial spread of second messenger signaling and can be expanded to simulate second messenger signals in the pulmonary vasculature.