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- ItemInfluence of cell shape, inhomogeneities and diffusion barriers in cell polarization models(Philadelphia, Pa. : IOP Publ., 2015) Giese, Wolfgang; Eigel, Martin; Westerheide, Sebastian; Engwer, Christian; Klipp, EddaIn silico experiments bear the potential for further understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results. Cell polarization and spatial reorganization of membrane proteins are fundamental for cell division, chemotaxis and morphogenesis. We chose the yeast Saccharomyces cerevisiae as an exemplary model system which entails the shuttling of small Rho GTPases such as Cdc42 and Rho, between an active membrane-bound form and an inactive cytosolic form. We used partial differential equations to describe the membrane-cytosol shuttling of proteins. In this study, a consistent extension of a class of 1D reaction-diffusion systems into higher space dimensions is suggested. The membrane is modeled as a thin layer to allow for lateral diffusion and the cytosol is modeled as an enclosed volume. Two well-known polarization mechanisms were considered. One shows the classical Turing-instability patterns, the other exhibits wave-pinning dynamics. For both models, we investigated how cell shape and diffusion barriers like septin structures or bud scars influence the formation of signaling molecule clusters and subsequent polarization. An extensive set of in silico experiments with different modeling hypotheses illustrated the dependence of cell polarization models on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. In particular, the results of our computer simulations suggested that for both mechanisms, local diffusion barriers on the membrane facilitate Rho GTPase aggregation, while diffusion barriers in the cytosol and cell protrusions limit spontaneous molecule aggregations of active Rho GTPase locally.
- ItemInfluence of cell shape, inhomogeneities and diffusion barriers in cell polarization models(Berlin : Weierstraß-Institut für Angewandte Analysis und Stochastik, 2014) Giese, Wolfgang; Eigel, Martin; Westerheide, Sebastian; Engwer, Christian; Klipp, EddaIn silico experiments bear the potential to further the understanding of biological transport processes by allowing a systematic modification of any spatial property and providing immediate simulation results for the chosen models. We consider cell polarization and spatial reorganization of membrane proteins which are fundamental for cell division, chemotaxis and morphogenesis. Our computational study is motivated by mating and budding processes of S. cerevisiae. In these processes a key player during the initial phase of polarization is the GTPase Cdc42 which occurs in an active membrane-bound form and an inactive cytosolic form. We use partial differential equations to describe the membrane-cytosol shuttling of Cdc42 during budding as well as mating of yeast. The membrane is modeled as a thin layer that only allows lateral diffusion and the cytosol is modeled as a volume. We investigate how cell shape and diffusion barriers like septin structures or bud scars influence Cdc42 cluster formation and subsequent polarization of the yeast cell. Since the details of the binding kinetics of cytosolic proteins to the membrane are still controversial, we employ two conceptual models which assume different binding kinetics. An extensive set of in silico experiments with different modeling hypotheses illustrate the qualitative dependence of cell polarization on local membrane curvature, cell size and inhomogeneities on the membrane and in the cytosol. We examine that spatial inhomogenities essentially determine the location of Cdc42 cluster formation and spatial properties are crucial for the realistic description of the polarization process in cells. In particular, our computer simulations suggest that diffusion barriers are essential for the yeast cell to grow a protrusion.