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Talk Abstract
The Virtual Cell

Leslie Loew, Univ. of Connecticut Health Center

The Virtual Cell is a fully modular general framework for modeling cell biological processes. An intuitive JAVA interface includes options for database access, geometry definition (including directly from experimental images), specification of compartment topology, species definition and assignment, chemical reaction input, and computational mesh. Deterministic and stochastic physical formulations have been implemented. The algorithms have been rigorously tested against exact solutions including various membrane and boundary conditions.

The Virtual Cell has been used to model calcium waves produced by InsP3-mediated release from endoplasmic reticulum (ER) in differentiated N1E-115 neuroblastoma cells. Experimentally, stimulation with 500 nM bradykinin produces waves that are non-oscillatory and start in the middle of the neurite following a latency of 3 seconds. The [Ca2+] increases to 1 µM within 1 second and decays to near baseline levels with a time constant of about 10s. A model was constructed based on the geometry of a cell for which the calcium wave had been experimentally imaged. The distributions of the relevant cellular components (InsP3R, SERCA pumps, bradykinin receptors, and ER) were based on 3D confocal immunofluorescence images. Biochemical and electrophysiological data on the rate of InsP3 production, InsP3R levels, the channel opening characteristics of the InsP3R, calcium flux through the InsP3R channel, binding to fixed and mobile buffers, and the rate of calcium-activated pumping by SERCA were all used to constrain the model. The simulation matched the spatial and temporal characteristics of the experimental calcium wave. It also provided new insights into mechanistic features underlying the wave and predicted the outcome of new experiments.

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