Explore the vast range of titles available.

Amperometry with ultramicroelectrodes is nowadays a routine technique to investigate neurotransmitter secretion by vesicular exocytosis at the single-cell level. This electroanalytical tool allows one to understand many aspects of the vesicular release in terms of mechanisms. However, the electrochemical detection relies on the oxidation of released neurotransmitters that produce 2H+ and thus the possible acidification of the cell-electrode cleft. In a previous work, we considered a model involving the H+ diffusion or/and its reaction with buffer species. In this article, we report a more general model which takes into account the ability of buffer species to move and to be regenerated within the cell-electrode cleft. As a consequence, the pH within the cleft is still equal to its physiological value regardless of the electrochemical detection of the vesicular release for usual exocytotic cell frequencies. This confirms that amperometry at the single-cell level is a very robust technique for investigating vesicular exocytosis.

We describe the construction of a fully tractable mathematical model for intracellular pH. This work is based on coupling the kinetic equations depicting the molecular mechanisms for pumps, transporters and chemical reactions, which determine this parameter in eukaryotic cells. Thus, our system also calculates the membrane potential and the cytosolic ionic composition. Such a model required the development of a novel algebraic method that couples differential equations for slow relaxation processes to steady-state equations for fast chemical reactions. Compared to classical heuristic approaches based on fitted curves and ad hoc constants, this yields significant improvements. This model is mathematically self-consistent and allows for the first time to establish analytical solutions for steady-state pH and a reduced differential equation for pH regulation. Because of its modular structure, it can integrate any additional mechanism that will directly or indirectly affect pH. In addition, it provides mathematical clarifications for widely observed biological phenomena such as overshooting in regulatory loops. Finally, instead of including a limited set of experimental results to fit our model, we show examples of numerical calculations that are extremely consistent with the wide body of intracellular pH experimental measurements gathered by different groups in many different cellular systems.

Motivated by a neuroscience question about synchrony detection in spike train analysis, we deal with the independence testing problem for point processes. We introduce nonparametric test statistics, which are rescaled general U-statistics, whose corresponding critical values are constructed from bootstrap and randomization/permutation approaches, making as few assumptions as possible on the underlying distribution of the point processes. We derive general consistency results for the bootstrap and for the permutation w.r.t. Wasserstein's metric, which induces weak convergence as well as convergence of second-order moments. The obtained bootstrap or permutation independence tests are thus proved to be asymptotically of the prescribed size, and to be consistent against any reasonable alternative. A simulation study is performed to illustrate the derived theoretical results, and to compare the performance of our new tests with existing ones in the neuroscientific literature.

In flows where the ratio of inertia to gravity varies strongly, large variations in the fluid thickness appear and hydraulic jumps arise, as depicted by Rayleigh. We report a new family of hydraulic jumps, where the capillary effects dominate the gravitational acceleration. The Bond number – which measures the importance of gravitational body forces compared to surface tension – must be small in order to observe such objects using capillarity as a driving force. For water, the typical length should be smaller than 3 mm. Nevertheless, for such small scales, solid boundaries induce viscous stresses, which dominate inertia, and capillary jumps should not be described by the inertial shock wave theory that one would deduce from Bélanger or Rayleigh for hydraulic jumps. In order to get rid of viscous shears, we consider Plateau borders, which are the microchannels defined by the merging of three films inside liquid foams, and we show that capillary jumps propagate along these deformable conduits. We derive a simple model that predicts the velocity, geometry and shape of such fronts. A strong analogy with Rayleigh’s description is pointed out. In addition, we carried out experiments on a single Plateau border generated with soap films to observe and characterize these capillary jumps. Our theoretical predictions agree remarkably well with the experimental measurements.

Phospholipid bilayers have been intensively studied by molecular dynamics (MD) simulation in recent years. The properties of bilayer edges are important in determining the structure and stability of pores formed in vesicles and biomembranes. In this work, we use molecular dynamics simulation to investigate the structure, dynamics, and line tension of the edges of bilayer ribbons composed of pure dimyristoylphosphatidylcholine (DMPC) or palmitoyl-oleoylphosphatidylethanolamine (POPE). As expected, we observe a significant reorganization of lipids at and near the edges. The treatment of electrostatic effects is shown to have a qualitative impact on the structure and stability of the edge, and significant differences are observed in the dynamics and structure of edges formed by DMPC and palmitoyl-oleoylphosphatidylethanolamine. From the pressure anisotropy in the simulation box, we calculate a line tension of ∼10–30 pN for the DMPC edge, in qualitative agreement with experimental estimates for similar lipids.

A significant number of exocytosis events recorded with amperometry demonstrate a prespike feature termed a “foot” and this foot has been correlated with messengers released via a transitory fusion pore before full exocytosis. We have compared amperometric spikes with a foot with spikes without a foot at chromaffin cells and found that the probability of detecting a distinct foot event is correlated to the amount of catecholamine released. The mean charge of the spikes with a foot was found to be twice that of the spikes without a foot, and the frequency of spikes displaying a foot was zero for small spikes increasing to ∼50% for large spikes. It is hypothesized that in chromaffin cells, where the dense core is believed to nearly fill the vesicle, the expanding core is a controlling factor in opening the fusion pore, that prefusion of two smaller vesicles leads to excess membrane, and that this slows pore expansion leading to an increased observation of events with a foot. Clearly, the physicochemical properties of vesicles are key factors in the control of the dynamics of release through the fusion pore and the high and variable frequency of this release makes it highly significant.

pH regulation of eukaryotic cells is of crucial importance and influences different mechanisms including chemical kinetics, buffer effects, metabolic activity, membrane transport and cell shape parameters. In this study, we develop a microfluidic system to rapidly and precisely control a continuous flow of ionic chemical species to acutely challenge the intracellular pH regulation mechanisms and confront predictive models. We monitor the intracellular pH dynamics in real-time using pH-sensitive fluorescence imaging and establish a robust mathematical tool to translate the fluorescence signals to pH values. By varying flow rate across the cells and duration for rinsing process, we manage to tweak the dynamics of intracellular pH from a smooth recovery to either an overshooting state, where the pH goes excitedly to a maximum value before decreasing to a plateau, or an undershooting state where the pH is unable to recover to ~7. We believe our findings will provide more insight into intracellular regulatory mechanisms and promote the possibility of exploring cellular behavior in the presence of strong gradients or fast changes in homogeneous conditions.

We have explored receding contact line dynamics on superhydrophobic surfaces, composed of micropillars arrays. We present here dynamic receding contact angle measurements of water on such surfaces, covering contact line speeds spanning over five decades. We have studied the effect of pillars fraction on dynamical receding contact angles. We compared these measurements to those on smooth surfaces with the same chemical nature and also with similar systems reported in the literature. We show that superhydrophobic surfaces exhibit a significantly lower dependence of contact angle on contact line speed compared to smooth surfaces. Additionally, we observed that a higher surface fraction of pillars leads to a greater dependence of the contact angle on contact line speed, approaching the dependence of the angle on smooth surface. Interestingly, we show that the exact texuration of the surface does not play a fundamental role in the angle-velocity relationships as long as microtextures present the same type of periodic pattern (pillar arrays or microgrid). These results are interpreted in terms of viscous friction reduction on superhydrophobic surfaces, shedding light on the underlying mechanisms governing their unique dynamic behavior. In addition we show that contact angles follow same laws for two different geometries (milimetric sessile drop and a centimetric capillary bridge).

Lithium (Li) has a wide range of uses in science, medicine and industry but its isotopy is underexplored, except in nuclear science and in geoscience. 6Li and 7Li isotopic ratio exhibits the second largest variation on Earth surface and constitutes a widely used tool for reconstructing past oceans and climates. As large variations have been measured in mammalian organs, plants or marine species, and as 6Li elicits stronger effects than natural Li (~95% 7Li) a central issue is the identification and quantification of biological influence of Li isotopes distribution. We show here that membrane ion channels and Na+-Li+/H+ exchangers (NHEs), strongly fractionate Li isotopes. This systematic 6Li enrichment is driven by membrane potential for channels, and by intracellular pH for NHEs, where it displays cooperativity, a hallmark of dimeric transport. Evidencing that transport proteins discriminate between isotopes differing by one neutron, opens new avenues for transport mechanisms, Li physiology, and paleoenvironments. Competing Interest Statement The authors have declared no competing interest.