Modeling cellular models

Cho MJ, DP Thompson, CT Cramer, T Vidmar, JF Scieszka. (1989). The Madin-Darby canine kidney (MDCK) epithelial cell monolayer as a model cellular transport barrier. Pharm Res 6 71-77. 

Wu, P.F., Wu, X.R, and Wainer, G., Applying cell-DEVS in 3D free-form shape modeling, Cellular Automata, Proceedings Lecture Notes in Computer Science (LNCS), Springer, Berlin, 3305,81, 2004. 

In this model, cellular stress mediates the release of cytochrome C from the mitochondrion. The proapoptotic proteins Bax and BH3 proteins support the release of cytochrome C, while the antiapoptotic Bcl2 protein has an inhibitory effect. Cytosolic cytochrome C binds to the cofactor Apaf 1, which then associates via its CARD motif with procaspase 9 to a complex termed apopto-some. In this complex, procaspase 9 is processed to the mature caspase which subsequently activates downstream effector caspases and commits the cell to death. 

In living cells the potential dynamically changes as different ion transporters and channels controlled by various mechanisms open and close. Approaches to and examples of modeling cellular electrophysiology are covered in greater depth in Chapter 7. 

The observed stability of this complex was thus adequate to assess this synthetic SOD mimic in a variety of in vitro and in vivo models of superoxide-mediated injury. Most notably this complex exhibits efficacy in in vitro and in vivo models of inflammation, myocardial ischemia-reperfusion injury, " and vascular relaxation and restenosis. In addition, this and other complexes of this class of SOD mimetics derived from I have superior properties to the SOD enzymes in regard to their normal dose-response curve (no deleterious effects observed at high doses in animal models), cellular permeability (dependent on the nature of the R groups), extended in vivo stability, nonimmunogenicity, and projected lower cost. 

Endy, D., and R. Brent. 2001. Modelling cellular behavior. Nature 409 391-5. 

Smith HW, Winstead CJ, Stank KK, Halstead BW, Wierda D. A predictive F344 rat immunotoxicology model cellular parameters combined with humoral responses to NP-CyG and KLH. Toxicology 2003 194 129-145. 

J. Schaff, C.C. Fink, B. Slepchenko, J.H. Carson, L.M. Loew, A general computational framework for modeling cellular structure and function, Biophys. J. 1997, 73, 1135-1146. 

Virus Disease Molecular level model Cellular level model... 

Due to its central role in toxicant metabolism, the liver is one of the first organs being constructed in the Virtual Tissue Research Project. Physiologically based pharmacokinetic modeling, cellular systems, and molecular networks are integrated to mimic the multitude of activities performed by the liver. Once completed, this innovative project will be an invaluable resource for accessible, accurate, and responsible prediction of liver toxicity. 

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