A Bistable Model of Cell Polarity

Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types

From autoimmune hepatitis to Q fever

Q fever is an infectious disease caused by Coxiella burnetii. Its clinical presentation is often nonspecific and the serological diagnosis difficult to make, especially in the absence of specific and suspected medical history. This article presents a case of fever of unknown origin (FUO), interpreted as an autoimmune hepatitis, later proven by the liver biopsy to be a granulomatous hepatitis caused by C. burnetii. The approach to FUO, the features of granulomatous hepatitis and Q fever are presented and discussed

Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

The growth of a well-formed epithelial structure is governed by mechanical constraints, cellular apico-basal polarity, and spatially controlled cell division. Here we compared the predictions of a mathematical model of epithelial growth with the morphological analysis of 3D epithelial structures. In both in vitro cyst models and in developing epithelial structures in vivo, epithelial growth could take place close to or far from mechanical equilibrium, and was determined by the hierarchy of time-scales of cell division, cell-cell rearrangements, and lumen dynamics. Equilibrium properties could be inferred by the analysis of cell-cell contact topologies, and the nonequilibrium phenotype was altered by inhibiting ROCK activity. The occurrence of an aberrant multilumen phenotype was linked to fast nonequilibrium growth, even when geometric control of cell division was correctly enforced. We predicted and verified experimentally that slowing down cell division partially rescued a multilumen phenotype induced by altered polarity. These results improve our understanding of the development of epithelial organs and, ultimately, of carcinogenesi

Fluctuating fast chemical reactions in a batch process modelled by stochastic differential equations

In this paper, we report on results of investigations of the effects of fluctuations in the kinetics of a batch chemical reactor on the time trend of both concentration and temperature. Mixing problems and the relevant lack of ideality in the stirred tank may produce inhomogeneity in the chemical and physical properties of the global reacting system. The process is modelled by a system of stochastic ordinary differential equations whose weak solution is numerically determined by the Euler-Maruyama method. In particular, the role of the reaction order and the amplitude of fluctuation is analysed with respect to the first order moments of the concentration and temperature, respectively. The simulations have pointed out a considerable bias between the solution of the deterministic problem and the corresponding first moment trend of the stochastic approach in cases of nonlinear kinetics. (C) 2006 Elsevier Ltd. All rights reserved

Prototypical model of cell polarization.

<p>A system of receptors transduces an external distribution of chemotactic cues into an internal distribution of activated enzymes , which catalyze the switch of a signaling molecule from an unactivated state to an activated state . A counteracting enzyme transforms the state back into . The network contains a couple of amplifying feedback loops: the signaling molecule activates and acvivates . The signaling molecules , are permanently bound to the cell surface and perform diffusive motions on it, while the , enzymes are free to shuttle between the cytosolic reservoir and the membrane. The result of the polarization process is the formation of separate domains with -rich patches and, respectively, -rich patches.</p