Entropic forces drive self-organization and membrane fusion by SNARE proteins

SNARE proteins are the core of the cell’s fusion machinery and mediate virtually all known intracellular membrane fusion reactions on which exocytosis and trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form trans-SNARE complexes (“SNAREpins”) with target membrane-associated t-SNAREs, a zippering-like process releasing ∼65 kT per SNAREpin. Fusion requires several SNAREpins, but how they cooperate is unknown and reports of the number required vary widely. To capture the collective behavior on the long timescales of fusion, we developed a highly coarse-grained model that retains key biophysical SNARE properties such as the zippering energy landscape and the surface charge distribution. In simulations the ∼65-kT zippering energy was almost entirely dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The SNAREpins self-organized into a circular cluster at the fusion site, driven by entropic forces that originate in steric–electrostatic interactions among SNAREpins and membranes. Cooperative entropic forces expanded the cluster and pulled the membranes together at the center point with high force. We find that there is no critical number of SNAREs required for fusion, but instead the fusion rate increases rapidly with the number of SNAREpins due to increasing entropic forces. We hypothesize that this principle finds physiological use to boost fusion rates to meet the demanding timescales of neurotransmission, exploiting the large number of v-SNAREs available in synaptic vesicles. Once in an unfettered cluster, we estimate ≥15 SNAREpins are required for fusion within the ∼1-ms timescale of neurotransmitter release

Analyzing the effects of surface distribution of pores in cell electroporation for a cell membrane containing cholesterol

This paper presents a model and numerical analysis (simulations) of transmembrane potential induced in biological cell membrane under the influence of externally applied electric field (i.e., electroporation). This model differs from the established models of electroporation in two distinct ways. Firstly, it incorporates the presence of cholesterol (~20% mole-fraction) in biological membrane. Secondly, it considers the distribution of pores as a function of the variation of transmembrane potential from one region of the cell to another. Formulation is based on the role of membrane tension and electrical forces in the formation of pores in a cell membrane, which is considered as an infinitesimally thin insulator. The model has been used to explore the process of creation and evolution of pores and to determine the number and size of pores as a function of applied electric field (magnitude and duration). Results show that the presence of cholesterol enhances poration by changing the membrane tension. Analyses indicate that the number of pores and average pore radii differ significantly from one part of the cell to the other. While some regions of the cell membrane undergo rapid and dense poration, others remain unaffected. The method can be a useful tool for a more realistic prediction of pore formation in cells subjected to electroporation.Comment: 11 pages, 3 figures. v2: added new references, grammatical changes, corrected typo

Strong tidal dissipation in Saturn and constraints on Enceladus' thermal state from astrometry

Tidal interactions between Saturn and its satellites play a crucial role in both the orbital migration of the satellites and the heating of their interiors. Therefore constraining the tidal dissipation of Saturn (here the ratio k2/Q) opens the door to the past evolution of the whole system. If Saturn's tidal ratio can be determined at different frequencies, it may also be possible to constrain the giant planet's interior structure, which is still uncertain. Here, we try to determine Saturn's tidal ratio through its current effect on the orbits of the main moons, using astrometric data spanning more than a century. We find an intense tidal dissipation (k2/Q= (2.3 \pm 0.7) \times 10-4), which is about ten times higher than the usual value estimated from theoretical arguments. As a consequence, eccentricity equilibrium for Enceladus can now account for the huge heat emitted from Enceladus' south pole. Moreover, the measured k2/Q is found to be poorly sensitive to the tidal frequency, on the short frequency interval considered. This suggests that Saturn's dissipation may not be controlled by turbulent friction in the fluid envelope as commonly believed. If correct, the large tidal expansion of the moon orbits due to this strong Saturnian dissipation would be inconsistent with the moon formations 4.5 Byr ago above the synchronous orbit in the Saturnian subnebulae. But it would be compatible with a new model of satellite formation in which the Saturnian satellites formed possibly over longer time scale at the outer edge of the main rings. In an attempt to take into account for possible significant torques exerted by the rings on Mimas, we fitted a constant rate da/dt on Mimas semi-major axis, also. We obtained an unexpected large acceleration related to a negative value of da/dt= -(15.7 \pm 4.4) \times 10-15 au/day

Domain Growth Kinetics in a Cell-sized Liposome

We investigated the kinetics of domain growth on liposomes consisting of a ternary mixture (unsaturated phospholipid, saturated phospholipid, and cholesterol) by temperature jump. The domain growth process was monitored by fluorescence microscopy, where the growth was mediated by the fusion of domains through the collision. It was found that an average domain size r develops with time t as r ~ t^0.15, indicating that the power is around a half of the theoretical expectation deduced from a model of Brownian motion on a 2-dimensional membrane. We discuss the mechanism of the experimental scaling behavior by considering the elasticity of the membrane

Model of SNARE-Mediated Membrane Adhesion Kinetics

SNARE proteins are conserved components of the core fusion machinery driving diverse membrane adhesion and fusion processes in the cell. In many cases micron-sized membranes adhere over large areas before fusion. Reconstituted in vitro assays have helped isolate SNARE mechanisms in small membrane adhesion-fusion and are emerging as powerful tools to study large membrane systems by use of giant unilamellar vesicles (GUVs). Here we model SNARE-mediated adhesion kinetics in SNARE-reconstituted GUV-GUV or GUV-supported bilayer experiments. Adhesion involves many SNAREs whose complexation pulls apposing membranes into contact. The contact region is a tightly bound rapidly expanding patch whose growth velocity increases with SNARE density . We find three patch expansion regimes: slow, intermediate, fast. Typical experiments belong to the fast regime where depends on SNARE diffusivities and complexation binding constant. The model predicts growth velocities s. The patch may provide a close contact region where SNAREs can trigger fusion. Extending the model to a simple description of fusion, a broad distribution of fusion times is predicted. Increasing SNARE density accelerates fusion by boosting the patch growth velocity, thereby providing more complexes to participate in fusion. This quantifies the notion of SNAREs as dual adhesion-fusion agents

Overview of first atmospheric results from InSight

The InSight spacecraft landed in the flat regions of Elysium Planitia on November 26th 2018. The instruments on board InSight make it capable of acting as a meteorological station at the surface of Mars. A pressure sensor (PS), two temperature and wind sensor booms (TWINS), along with the InSight FluxGate (IFG) magnetometer, form the Auxiliary Sensor Payload Suite (APSS). This is complemented by capabilities to measure surface brightness temperature by the radiometer in the Heat-Flow and Physical Properties Package (HP3) suite, to explore the impact of atmospheric processes on seismic measurements by SEIS, and to use InSight cameras to estimate atmospheric opacity (notably caused by suspended dust particles) and other atmospheric phenomena such as clouds and dust devils. We will discuss results drawn from atmospheric measurements on board InSight over the first two months of operation, highlighting new perspectives permitted by the high-frequency, continuous nature of the InSight acquisitions. Surface pressure measurements record global-to-local atmospheric phenomena: CO2 condensation (annual), dust cycle and storms (seasonal), baroclinic waves (weekly), thermal tides (daily), gravity waves (thousands of seconds), convective cells (hundreds of seconds), convective vortices (tens of seconds, leading to dust devils if dust particles are transported in the vortex). Two main large-scale wind regimes were expected from Global Climate Modeling at the InSight landing site during a typical year: towards the northwest in northern spring and summer, then in the opposite direction in southern summer. Existing in-situ measurements on Mars and Large-Eddy Simulations indicate that daytime convective vortices and cells not only impact pressure, but also temperature and winds; the nighttime atmosphere on Mars is comparatively much less turbulent and dominated by shear-driven turbulence, in contrast to the buoyancy-driven turbulence active in daytime. All such existing measurements and model predictions will be compared and challenged with InSight measurements. Seismic signatures associated with atmospheric phenomena will also be discussed, with a particular emphasis on the knowledge gained by the unprecedented measurements performed by InSight’s seismometers

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

First Atmospheric Results from InSight APSS

NASA’s Mars InSight Spacecraft landed on Nov 26, 2018 (Ls=295°) in Elysium Planitia (~4.5°N, 136°E). InSight’s main scientific purpose is to investigate the interior structure and heat flux from Mars, but it is also equipped with instrumentation that can serve as a very capable meteorological station. To remove unwanted environmental noise from the seis- mic signals, InSight carries a very precise pressure sensor (PS) and the first magnetometer (IFG) to the surface of Mars. Additionally, to aid in removing the atmospheric pressure-induced seismic noise, and to identify periods when wind-induced seismic noise may reduce sensitivity, InSight also carries a pair of Wind and Air temperature sensors (TWINS). These three sensors comprise the Auxiliary Payload Sensor Suite (APSS) [1]. Complementing this are a radiometer in the HP3 suite to measure surface radiance, the seismic measurements of SEIS which can record interesting atmospheric phenomena, and the InSight cameras to image clouds and dust devils and estimate atmospheric opacity from dust or clouds. The Lander also carried accelerometers that can be used to reconstruct the at- mospheric structure during descent. We will discuss results drawn from atmospheric measurements on board InSight from the first months of operation, high- lighting the new perspectives permitted by the novel high-frequency, and continuous nature of the InSight data acquisition. Details on pre-landing scientific perspectives for atmospheric science with InSight are found in [2]

Pupillary Stroop effects

We recorded the pupil diameters of participants performing the words’ color-naming Stroop task (i.e., naming the color of a word that names a color). Non-color words were used as baseline to firmly establish the effects of semantic relatedness induced by color word distractors. We replicated the classic Stroop effects of color congruency and color incongruency with pupillary diameter recordings: relative to non-color words, pupil diameters increased for color distractors that differed from color responses, while they reduced for color distractors that were identical to color responses. Analyses of the time courses of pupil responses revealed further differences between color-congruent and color-incongruent distractors, with the latter inducing a steep increase of pupil size and the former a relatively lower increase. Consistent with previous findings that have demonstrated that pupil size increases as task demands rise, the present results indicate that pupillometry is a robust measure of Stroop interference, and it represents a valuable addition to the cognitive scientist’s toolbox