Biomedical subjects

Silvina Ponce Dawson

Publications and source records attributed to Silvina Ponce Dawson.

9 recordsLinked to original sources

PubMed2006

Simple data-driven models of intracellular calcium dynamics with predictive power.

Biology is complex. However, it is not clear how much of this complexity must necessarily translate into complicated mathematical models of biological processes. Simple models can be appealing to physicists but are usually deceiving for biologists. Complicated models, on the other hand, depend on too many parameters whose values are frequently unknown. Therefore, complicated models, although in principle more realistic, can lead to erroneous results if they are sensitive to these unknown parameter values. Intracellular calcium signals provide an example of utmost biological importance in which the issue of "simple vs complex" can be explored. In this paper we show that simple models describing the dynamics of intracellular calcium can be directly inferred from experimental data, without no a priori information on unknown parameters. A similar approach can be followed to study other reaction-diffusion systems. In spite of their simplicity, these models can provide quantitative information on some of the processes that shape calcium signals, such as the calcium current that underlies an experimental observation. This shows that simple models of biological systems are not limited to qualitative descriptions.

Animals↗

PubMed2006

Messages diffuse faster than messengers.

In many cell-signaling pathways, information is transmitted by the diffusion of messenger molecules. Diffusion coefficients characterize the messenger's spatial range and the characteristic times of signal propagation. Inside cells, particles usually diffuse in the presence of immobile binding sites (or traps). It is well known that binding to traps results in an effective diffusion coefficient that is smaller than the free coefficient in media free of traps. To measure effective diffusion coefficients in cells, "tagged" particles are often used. Radioactive calcium was used in a giant squid axon and in cytosolic extracts of Xenopus laevis oocytes. Fluorescence recovery after photobleaching yields diffusion coefficients from observations of the distribution of fluorescently labeled proteins. In the absence of traps, free diffusion coefficients give both the rate at which single-particle mean square displacements increase and the rate at which information in the form of inhomogeneities in particle concentration spread out with time. We show here that, in the presence of traps, information diffuses faster than single particles. Thus, messages diffuse faster than messengers. Tagged-particle experiments give the single-particle diffusion coefficients and, thus, can underestimate the rate of diffusive signal propagation.

Animals↗

PubMed2006

Analysis of puff dynamics in oocytes: interdependence of puff amplitude and interpuff interval.

Puffs are localized Ca(2+) signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP(3)). They are analogous to the sparks of myocytes and are believed to be the result of the liberation of Ca(2+) from the endoplasmic reticulum through the coordinated opening of IP(3) receptor/channels clustered at a functional release site. In this article, we analyze sequences of puffs that occur at the same site to help elucidate the mechanisms underlying puff dynamics. In particular, we show a dependence of the interpuff time on the amplitude of the preceding puff, and of the amplitude of the following puff on the preceding interval. These relationships can be accounted for by an inhibitory role of the Ca(2+) that is liberated during puffs. We construct a stochastic model for a cluster of IP(3) receptor/channels that quantitatively replicates the observed behavior, and we determine that the characteristic time for a channel to escape from the inhibitory state is of the order of seconds.

Animals↗

PubMed2005

A model-independent algorithm to derive Ca2+ fluxes underlying local cytosolic Ca2+ transients.

Local intracellular Ca(2+) signals result from Ca(2+) flux into the cytosol through individual channels or clusters of channels. To gain a mechanistic understanding of these events we need to know the magnitude and spatial distribution of the underlying Ca(2+) flux. However, this is difficult to infer from fluorescence Ca(2+) images because the distribution of Ca(2+)-bound dye is affected by poorly characterized processes including diffusion of Ca(2+) ions, their binding to mobile and immobile buffers, and sequestration by Ca(2+) pumps. Several methods have previously been proposed to derive Ca(2+) flux from fluorescence images, but all require explicit knowledge or assumptions regarding these processes. We now present a novel algorithm that requires few assumptions and is largely model-independent. By testing the algorithm with both numerically generated image data and experimental images of sparklets resulting from Ca(2+) flux through individual voltage-gated channels, we show that it satisfactorily reconstructs the magnitude and time course of the underlying Ca(2+) currents.

Algorithms↗

PubMed2004

Role of complexing agents in the appearance of Turing patterns.

In this paper we study a four-species reaction-diffusion system where Turing patterns are stabilized by the presence of fast reversible reactions between the morphogens and two different mobile complexing agents (CAs) that are not necessarily in excess. We provide a quantitative explanation of how the interaction with the CA changes the size of the Turing space making it possible to observe patterns even in a region where the free diffusion coefficients of the relevant species are equal, as is usually the case in real systems. Our analytical treatment gives a series of mathematical relations that can be helpful for those designing experiments where Turing patterns are expected to appear. We also show how the mobility of CAs affect the characteristic size of the pattern. Finally, we provide an example of biological interest in order to illustrate the main procedures and results.

Biophysics↗

PubMed2004

A model of IP3 receptor with a luminal calcium binding site: stochastic simulations and analysis.

We have constructed a stochastic model of the inositol 1,4,5-trisphosphate receptor-Ca2+ channel that is based on quantitative measurements of the channel's properties. It displays the observed dependence of the open probability of the channel with cytosolic [Ca2+] and [IP3] and gives values for the dwell times that agree with the observations. The model includes an explicit dependence of channel gating with luminal calcium. This not only explains several observations reported in the literature, but also provides a possible explanation of why the open probabilities and shapes of the bell-shaped curves reported in [Nature 351 (1991) 751] and in [Proc. Natl. Acad. Sci. U.S.A. 269 (1998) 7238] are so different.

Binding Sites↗

PubMed2003

Sheet excitability and nonlinear wave propagation.

In the Xenopus laevis oocyte, calcium ion channels are clustered in a thin shell. Motivated by this morphology, we study a general class of reaction-diffusion systems that include most of the well-known models that support wave propagation but restricting excitability to a "sheet" of codimension 1. We find waves that undergo propagation failure with increasing diffusion coefficient and a scaling regime in which the wave speed is independent of it.

Animals↗

PubMed2003

Saltatory and continuous calcium waves and the rapid buffering approximation.

Calcium waves propagate inside cells due to a regenerative mechanism known as calcium-induced calcium release. Buffer-mediated calcium diffusion in the cytosol plays a crucial role in the process. However, most models of calcium waves either treat buffers phenomenologically or assume that they are in equilibrium with calcium (the rapid buffering approximation). In this article we address the issue of whether this approximation provides a good description of wave propagation. We first compare the timescales present in the problem, and determine the situations in which the equilibrium hypothesis fails. We then present a series of numerical studies based on the simple fire-diffuse-fire model of wave propagation. We find that the differences between the full and reduced descriptions may lead to errors that are above experimental resolution even for relatively fast buffers in the case of saltatory waves. Conversely, in the case of continuous waves, the approximation may give accurate results even for relatively slow buffers.

Biophysics↗

PubMed2002

Slow time evolution of two-time-scale reaction-diffusion systems: the physical origin of nondiffusive transport.

We study, from a mesoscopic point of view, the slow time-scale dynamics of a mixture of chemicals in which there is a chemical reaction that occurs much faster than all other processes, including diffusion. For a simple paradigmatic model reaction, it is possible to find a reduced set of dynamical equations analytically. This procedure, which yields the same mean field equations as the macroscopic approach described by Strier and Dawson [J. Chem. Phys, 112, 825 (2000)], clarifies the physical origin of some of the terms that appear in the reduced reaction-diffusion equations, such as "negative density dependent cross diffusion terms," whose actual meaning is hard to assess within the macroscopic framework. We also present a two-time-scale reactive lattice gas automaton with which it is possible to check the validity of the analytical results and the conditions under which the reduced description holds. Using this lattice gas we also show how the differential interaction with immobile species can give rise to the formation of stable Turing patterns in a system where all the other chemicals diffuse approximately at the same rate.

Journal Article↗