Morphology, Motility, and Signaling Morphology and Signaling

Combining experimental data and computer modeling, Fink et al. (page 929) demonstrate that cellular geometry is important in the spatiotemporal control of intracellular signaling. The researchers examined the dynamics of inositol-1,4,5-trisphosphate (InsP 3 )-mediated calcium signaling in neuroblastoma cells with complex morphology, and also simulated InsP 3 signaling in a computer model called Virtual Cell. The close agreement between the experimental data and the computer model suggest that Virtual Cell could be applied to a broad range of problems in cell biology. In an initial series of experiments, the team found that the neuroblastoma cell’s neurite produces a higher InsP 3 signal than the soma, and that the higher concentration of InsP 3 in the neurite is required for initiating a wave of calcium release. The computer model, which integrates experimental data on the geometric, biochemical, and electrophysiological components of the system, allowed the researchers to simulate the same phenomenon while altering a variety of parameters. These simulations suggest that because InsP 3 is produced from the plasma membrane, the high surface-to-volume ratio of the neurite causes the InsP 3 signal to reach a higher level in the neurite than in the soma. Conversely, the soma has a greater density of endoplasmic reticulum than the neurite, making the soma release more calcium than the neurite for a given amount of InsP 3 . The team is now using Virtual Cell to simulate a variety of other intracellular and intercellular signaling events (http://www.nrcam.uchc.edu).