Biomedical subjects

Jean-François Mercier

Publications and source records attributed to Jean-François Mercier.

6 recordsLinked to original sources

PubMed2006

Effective molecular diffusion coefficient in a two-phase gel medium.

We derive a mean-field expression for the effective diffusion coefficient of a probe molecule in a two-phase medium consisting of a hydrogel with large gel-free solvent inclusions, in terms of the homogeneous diffusion coefficients in the gel and in the solvent. Upon comparing with exact numerical lattice calculations, we find that our expression provides a remarkably accurate prediction for the effective diffusion coefficient, over a wide range of gel concentration and relative volume fraction of the two phases. Moreover, we extend our model to handle spatial variations of viscosity, thereby allowing us to treat cases where the solvent viscosity itself is inhomogeneous. This work provides robust grounds for the modeling and design of multiphase systems for specific applications, e.g., hydrogels as novel food agents or efficient drug-delivery platforms.

Journal Article↗

PubMed2006

Universal interpolating function for the dispersion coefficient of DNA fragments in sieving matrices.

The separation of DNA fragments by (slab or capillary) gel electrophoresis has been studied extensively. To characterize the separation achieved by such systems, one needs to understand the impact (and their dependency upon the experimental quantities) of two physical parameters: the electrophoretic mobility mu and the diffusion coefficient D. Three different regimes have been shown to exist for both mu and D: the Ogston regime, the reptation regime and the reptation with orientation regime (note that separation is only possible for the first two regimes). In the small electric field limit, both mu and D are apparently well described by theories for all three regimes. Unfortunately this results in disjointed scaling laws and no theory-based general equations can apply to all regimes. Recently, an empirical interpolating formula has been proposed that adequately fits the low electric field mobility mu of dsDNA fragments across all three regimes and is compatible with accepted theories. In this article we review and clarify the current state of knowledge regarding the size dependence of the mobility and the diffusion coefficient and propose an interpolating formula for molecular size dependence of the low field diffusion coefficient D. With formulas for both the mobility and the diffusion coefficient as a function of the experimental conditions one could, in principle, optimize any gel/polymer matrix-based electrophoresis system for a wide range of DNA molecular sizes.

DNA↗

PubMed2005

Solid phase DNA amplification: a Brownian dynamics study of crowding effects.

Solid phase amplification (SPA), a new method to amplify DNA, is characterized by the use of surface-bound primers. This limits the amplification to two-dimensional surfaces and therefore allows the easy parallelization of DNA amplification in a single system. SPA leads to the formation of small but dense DNA brushes, called DNA colonies. For a molecule to successfully duplicate itself, it needs to bend so that its free end can find a matching primer, located on the surface. We used Brownian dynamics simulations (with a united-atom model) to model the basic kinetics of an SPA experiment. The simulations mimic the temperature cycles and the molecule duplication process found in SPA. Our results indicate that the steric interaction between molecules leads to a decreased duplication probability for molecules in the center of a colony and to an outward leaning for the molecules on the perimeter. These effects result in slower amplification (compared to solution PCR) and indicate that steric interaction alone can explain the loss of the exponential growth (characteristic of solution PCR) of the number of molecules in an SPA experiment. Furthermore, the growth of the colony as a function of the number of thermal cycles is found to be similar to the one obtained with a simple Monte Carlo simulation.

Algorithms↗

PubMed2004

Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting.

Although homodimerization has been demonstrated for a large number of G protein-coupled receptors (GPCRs), no general role has been attributed to this process. Because it is known that oligomerization plays a key role in the quality control and endoplasmic reticulum (ER) export of many proteins, we sought to determine if homodimerization could play such a role in GPCR biogenesis. Using the beta2-adrenergic receptor (beta2AR) as a model, cell fractionation studies revealed that receptor homodimerization is an event occurring as early as the ER. Supporting the hypothesis that receptor homodimerization is involved in ER processing, beta2AR mutants lacking an ER-export motif or harboring a heterologous ER-retention signal dimerized with the wild-type receptor and inhibited its trafficking to the cell surface. Finally, in addition to inhibiting receptor dimerization, disruption of the putative dimerization motif, 276GXXXGXXXL284, prevented normal trafficking of the receptor to the plasma membrane. Taken together, these data indicate that beta2AR homodimerization plays an important role in ER export and cell surface targeting.

Binding Sites↗

PubMed2002

Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer.

Quantitative bioluminescence resonance energy transfer (BRET) analysis was applied to the study of beta(1)- and beta(2)-adrenergic receptor homo- and heterodimerization. To assess the relative affinity between each of the protomers, BRET saturation experiments were carried out in HEK-293T cells. beta(1)- and beta(2)-adrenergic receptors were found to have similar propensity to engage in homo- and heterotropic interactions suggesting that, at equivalent expression levels of the two receptor subtypes, an equal proportion of homo- and heterodimers would form. Analysis of the data also revealed that, at equimolar expression levels of energy donor and acceptor, more than 80% of the receptor molecules exist as dimers and that this high incidence of receptor dimerization is insensitive to receptor density for expression levels varying between 1.4 and 26.9 pmol of receptor/mg of membrane protein. Taken together, these results indicate that most of the receptors expressed in cells exist as constitutive dimers and that, at least in undifferentiated fibroblasts, the proportion of homo- and heterodimers between the closely related beta(1)- and beta(2)-adrenergic receptors is determined by their relative levels of expression.

Cell Line↗

PubMed2002

Theory of DNA electrophoresis (approximately 1999-2002(1/2)).

Over the last two decades, the introduction of new methods such as pulsed-field gel electrophoresis and capillary array electrophoresis has made it possible to map and sequence entire genomes, including our own. The development of these experimental methods has been helped by the progress of theoretical and computational sciences, and the interactions between these three modi operandi of modern science are still pushing the limits of our technologies. We now see a clear trend towards proteomics and microfluidic (even nanofluidic!) devices. In this review, we take a look at the progress of the field over the last 3 years using the glasses of the theoretical scientist and focusing mostly on new ideas and concepts. About a dozen different subfields are discussed and reviewed. We conclude by giving a commented list of some of the best review articles published over the last 2-3 years.

Animals↗